[Objective] To explore the polymorphism of the 3′ flank region of equine IGF-Ⅰ gene. [Method] The 3′ flank region sequences of IGF-Ⅰ gene were amplified from genomic DNA of 270 horses, which included 4 types of Mo...[Objective] To explore the polymorphism of the 3′ flank region of equine IGF-Ⅰ gene. [Method] The 3′ flank region sequences of IGF-Ⅰ gene were amplified from genomic DNA of 270 horses, which included 4 types of Mongolian horse, Sanhe horse and Thoroughbred, and then analyzed by PCR-SSCP. [Result] Three genotypes (AA, BB and AB) were detected by PCR-SSCP and the distribution of genotypes of all research objects except Xinihe horse and Baerhu horse were in line with the "Hardy-Weinberg Law". [Conclusion] There was a polymorphic locus in the 3′ flank region of IGF-Ⅰ gene, which might affect the equine growth and development mechanism. The study is of important theoretical and practical significance to improve the performance and to develop equine industry.展开更多
By employing different gel components and electrophoresis conditions, the PCR-SSCP(polymerase chain reaction-single-stranded conformation polymorphism) method was used to detect the polymorphism(CCC or CGC ) of codon ...By employing different gel components and electrophoresis conditions, the PCR-SSCP(polymerase chain reaction-single-stranded conformation polymorphism) method was used to detect the polymorphism(CCC or CGC ) of codon 72 in exon 4 of p53 gene. The results展开更多
Polymorphisms of porcine ob exon 1 and exon 2 among different breeds including Landrace, Duroc, Min pig, Yorkshire pig, double-muscled Yorkshire, Sanjiang pig, wild boar and cross bred pig were analyzed by PCR-SSCP in...Polymorphisms of porcine ob exon 1 and exon 2 among different breeds including Landrace, Duroc, Min pig, Yorkshire pig, double-muscled Yorkshire, Sanjiang pig, wild boar and cross bred pig were analyzed by PCR-SSCP in the current study. Three pairs of primers according to the ob cDNA sequence obtained from GenBank database were designed to amplify the first two exons, which were then genotyped by SSCP. The T to C transversion was found in exon 2, which resulted in 3 genotypes named AA, AB and BB, respectively in these different porcine breeds. There was only genotype of BB in the Min pig, while no allele B was detected in double-muscled Yorkshire, and the 3 genotypes all existed in other breeds. There was significant difference on the genotype frequencies in various breeds. There was a trend that the frequency of allele A was positively associated with muscle ratio distribution on the one hand, and on the other hand, it was linked to the selected direction. So the allele A could be used as a selective marker of high muscle ratio in pig breeding.展开更多
The rRNA genetic locus is found in all prokaryotic organisms, and is highly conservative, although its relatively stable variations are found frequently in different bacteria. The utility of this locus as a taxonomic ...The rRNA genetic locus is found in all prokaryotic organisms, and is highly conservative, although its relatively stable variations are found frequently in different bacteria. The utility of this locus as a taxonomic and phylogenetic tool has been reported widely. This study, aimed at 16S rRNA gene (16S rDNA) and with the help of biomolecular methods, attempted to achieve the goal of rapid identification of common pathogens. In this study, 333 clinical isolated pathogenic bacteria were collected. Two pairs of primers were chosen and labeled with different fluorescent dyes and then used to amplify the genomic DNA extracted from bacteria. The PCR products were then detected by capillary electrophoresis-single strand conformation polymorphism (CE-SSCP). In order to pursue higher resolution and peak-separation effect, a high efficient separating medium, liner polyacrylamidedel (LPA), was put to use in this study. Finally, every bacteria colony generated distinct patterns from each other, which were easily to be used for identification. These results indicated that PCR-CE-SSCP was a rapid identification method for bacterial identification, with the aspects of high efficiency and high precision. Compared with traditional method, this technology is of great utility for clinical use especially for its high sensitivity.展开更多
Objective: To study the relationship between the polymorphism of drug resistant gene rpoB and drug resistance against rifampicin(RFP) of M. tuberculosis L-forms, and to evaluate its clinical application. Methods: A to...Objective: To study the relationship between the polymorphism of drug resistant gene rpoB and drug resistance against rifampicin(RFP) of M. tuberculosis L-forms, and to evaluate its clinical application. Methods: A total of 52 clinical isolated strains of M. tuberculosis L-forms were collected. rpoB gene polymorphism was analyzed by polymerase chain reaction and single-strand conformation polymorphism (PCR-SSCP) and conventional antimicrobial susceptibility test (AST). Their results were compared. Results: AST results showed that 38 of 52 clinical isolated strains were drug resistance (73.08％),while PCR-SSCP indicated 65.38％ (32/52) rpoB gene polymorphism. There was no statistic significance(χ2= 2.4914) between the 2 methods. Conclusion:Combined the application of PCR-SSCP with AST in detecting rpoB drug resistant gene polymorphism of M. tuberculosis L-form from pneumoconiosis patients with tuberculosis may have advantages at earlier diagnosis and guidance of clinical medications.展开更多
BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis th...BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis through binding to dif-ferent ligands.AIM To evaluate the correlation between single nucleotide polymorphisms(SNPs)of ACVR1C and susceptibility to esophageal squamous cell carcinoma(ESCC)in Chinese Han population.METHODS In this hospital-based cohort study,1043 ESCC patients and 1143 healthy controls were enrolled.Five SNPs(rs4664229,rs4556933,rs77886248,rs77263459,rs6734630)of ACVR1C were assessed by the ligation detection reaction method.Hardy-Weinberg equilibrium test,genetic model analysis,stratified analysis,linkage disequi-librium test,and haplotype analysis were conducted.RESULTS Participants carrying ACVR1C rs4556933 GA mutant had significantly decreased risk of ESCC,and those with rs77886248 TA mutant were related with higher risk,especially in older male smokers.In the haplotype analysis,ACVR1C Trs4664229Ars4556933Trs77886248Crs77263459Ars6734630 increased risk of ESCC,while Trs4664229Grs4556933Trs77886248Crs77263459Ars6734630 was associated with lower susceptibility to ESCC.CONCLUSION ACVR1C rs4556933 and rs77886248 SNPs were associated with the susceptibility to ESCC,which could provide a potential target for early diagnosis and treatment of ESCC in Chinese Han population.展开更多
Subtropical evergreen broad-leaved trees are usually vulnerable to freezing stress,while hexaploid wild Camellia oleifera shows strong freezing tolerance.As a valuable genetic resource of woody oil crop C.oleifera,wil...Subtropical evergreen broad-leaved trees are usually vulnerable to freezing stress,while hexaploid wild Camellia oleifera shows strong freezing tolerance.As a valuable genetic resource of woody oil crop C.oleifera,wild C.oleifera can serve as a case for studying the molecular bases of adaptive evolution to freezing stress.Here,47 wild C.oleifera from 11 natural distribution sites in China and 4 relative species of C.oleifera were selected for genome sequencing.“Min Temperature of Coldest Month”(BIO6)had the highest comprehensive contribution to wild C.oleifera distribution.The population genetic structure of wild C.oleifera could be divided into two groups:in cold winter(BIO6≤0℃)and warm winter(BIO6>0℃)areas.Wild C.oleifera in cold winter areas might have experienced stronger selection pressures and population bottlenecks with lower N_(e) than those in warm winter areas.155 singlenucleotide polymorphisms(SNPs)were significantly correlated with the key bioclimatic variables(106 SNPs significantly correlated with BIO6).Twenty key SNPs and 15 key copy number variation regions(CNVRs)were found with genotype differentiation>50%between the two groups of wild C.oleifera.Key SNPs in cis-regulatory elements might affect the expression of key genes associated with freezing tolerance,and they were also found within a CNVR suggesting interactions between them.Some key CNVRs in the exon regions were closely related to the differentially expressed genes under freezing stress.The findings suggest that rich SNPs and CNVRs in polyploid trees may contribute to the adaptive evolution to freezing stress.展开更多
BACKGROUND Fluoropyrimidines are metabolized in the liver by the enzyme dihydropyrimidine dehydrogenase(DPD),encoded by the DPYD gene.About 7%of the European population is a carrier of DPYD gene polymorphisms associat...BACKGROUND Fluoropyrimidines are metabolized in the liver by the enzyme dihydropyrimidine dehydrogenase(DPD),encoded by the DPYD gene.About 7%of the European population is a carrier of DPYD gene polymorphisms associated with reduced DPD enzyme activity.AIM To assess the prevalence of DPYD polymorphisms and their impact on fluoropyrimidine tolerability in Italian patients with gastrointestinal malignancies.METHODS A total of 300 consecutive patients with a diagnosis of gastrointestinal malignancy and treated with a fluoropyrimidine-based regimen were included in the analysis and divided into two cohorts:(1)149 patients who started fluoropyrimidines after DPYD testing;and(2)151 patients treated without DPYD testing.Among the patients in cohort A,15%tested only the DPYD2A polymorphism,19%tested four polymorphisms(DPYD2A,HapB3,c.2846A>T,and DPYD13),and 66%tested five polymorphisms including DPYD6.RESULTS Overall,14.8%of patients were found to be carriers of a DPYD variant,the most common being DPYD6(12.1%).Patients in cohort A reported≥G3 toxicities(P=0.00098),particularly fewer nonhematological toxicities(P=0.0028)compared with cohort B,whereas there was no statistically significant difference between the two cohorts in hematological toxicities(P=0.6944).Significantly fewer chemotherapy dose reductions(P=0.00002)were observed in cohort A compared to cohort B,whereas there was no statistically significant differences in chemotherapy delay.CONCLUSION Although this study had a limited sample size,it provides additional information on the prevalence of DPYD polymorphisms in the Italian population and highlights the role of pharmacogenetic testing to prevent severe toxicity.展开更多
In our work,polymorphism strategy has been successfully applied to tune up chromism and luminescence properties of viologen-based materials.Two polymorphs of viologen-based complexes ofα-CdBr_(2)(PHSQ)_(2)(H_(2)O)_(2...In our work,polymorphism strategy has been successfully applied to tune up chromism and luminescence properties of viologen-based materials.Two polymorphs of viologen-based complexes ofα-CdBr_(2)(PHSQ)_(2)(H_(2)O)_(2)(1)andβ-CdBr_(2)(PHSQ)_(2)(H_(2)O)_(2)(2)(PHSQ=N-(4-sulfophenyl)-4,4-bipyridinium)were synthesized by changing the solvent.They can both respond to UV light and electricity in the manner of chromism visible to the naked eye and the coloration states have good reversibility,through which an inkless erasable printing model has been established.But the coloration contrast of 1 is higher compared to 2.Meanwhile,they both exhibit photoluminescence properties and the intensity of 1 is twice that of 2,which is accompanied by photoquenching upon continuous UV light irradiation.The only divergence of disordered/ordered O atoms in the two crystalline compounds leads to significantly different chromic and luminescent properties.Further explorations simultaneously demonstrate that the different chromic performance between 1 and 2 should attribute to the alteration of stimulus-induced(light/electricity)electron transfer channels caused by the ordered/disordered O atoms in the complexes,which is achieved through C-H···O and O-H···O interactions to change crystal arrangement and structural rigidity,thus affect luminescent properties.展开更多
Chinese hamster with Chinese characteristics is used in experiments,and it is of great value in the field of medical biology research.However,at present,there is no high-efficiency method for evaluating the genetic qu...Chinese hamster with Chinese characteristics is used in experiments,and it is of great value in the field of medical biology research.However,at present,there is no high-efficiency method for evaluating the genetic quality of Chinese hamsters.Here,we developed a novel Chinese hamster genetic quality detection system using single-nucleotide polymorphism(SNP)markers.To find SNP loci,we conducted whole genome sequencing on 24 Chinese hamsters.Then,we employed an SNP locus screening criterion that we set up previously and initially screened 214 SNP loci with wide genome distribution and high polymorphism level.Subsequently,we developed the SNP detection system using a multitarget region capture technique based on second-generation sequencing,and a 55 SNP panel for genetic evaluation of Chinese hamster populations was developed.PopGen.32.analysis results showed that the average effective allele number,Shannon index,observed heterozygosity,expected heterozygosity,average heterozygosity,polymorphism information,and other genetic parameters of Chinese hamster population A were higher than those in population B.Using scientific screening and optimization,we successfully developed a novel Chinese hamster SNP genetic detection system that can efficiently and accurately analyze the genetic quality of the Chinese hamster population.展开更多
Methylenetetrahydrofolate reductase(MTHFR)is a key enzyme in folate metabolism.Its genetic polymorphisms affect the metabolism of methyl donors,including folate and betaine,and are consequently associated with the dev...Methylenetetrahydrofolate reductase(MTHFR)is a key enzyme in folate metabolism.Its genetic polymorphisms affect the metabolism of methyl donors,including folate and betaine,and are consequently associated with the development of various chronic diseases such as stroke and neoplasms.Methods This umbrella review,covering the period from 2006 to 2025,searched PubMed,Embase,Web of Science,Medline,CNKI,WanFang,and Cochrane Library databases for published systematic reviews and meta-analyses of polymorphisms relating to the MTHFR C677T and A1298C gene polymorphisms and various chronic diseases.Subsequently,this study assessed methodological quality with AMSTAR-2,while the strength of evidence for each outcome was graded according to the GRADE and the credibility evaluation.This umbrella review included 39 studies related to 8 diseases classified according to the ICD-10 classification.Results Overall,C677T exhibited a positive correlation with depression(allele:OR=1.18,95%CI:1.13-1.24;dominant:OR=1.16,95%CI:1.09-1.23;recessive:OR=1.42,95%CI:1.30-1.56;homozygote:OR=1.48,95%CI:1.34-1.63),and polycystic ovary syndrome(allele:OR=1.35,95%CI:1.24-1.46;dominant:OR=1.46,95%CI:1.30-1.64;recessive:OR=1.39,95%CI:1.19-1.62;homozygote:OR=1.63,95%CI:1.38-1.93),and exhibited a negative correlation with oral cancer(allele:OR=0.24,95%CI:0.22-0.26;dominant:OR=0.14,95%CI:0.12-0.16;recessive:OR=0.31,95%CI:0.28-0.35;homozygote:OR=0.14,95%CI:0.12-0.16).A1298C was positively associated with polycystic ovary syndrome in four models(allele:OR=1.93,95%CI:1.67-2.21;dominant:OR=1.93,95%CI:1.64-2.27;recessive:OR=3.72,95%CI:2.47-5.61;homozygote:OR=4.38,95%CI:2.90-6.62).Conclusion The MTHFR C677T and A1298C gene polymorphisms demonstrated significant associations with non-communicable diseases,thereby contributing to the advancement of precision medicine.展开更多
BACKGROUND There are conflicting results on the potential correlation between folic acid and gestational diabetes mellitus(GDM),and the correlation between genetic factors related to folic acid metabolism pathways and...BACKGROUND There are conflicting results on the potential correlation between folic acid and gestational diabetes mellitus(GDM),and the correlation between genetic factors related to folic acid metabolism pathways and GDM remains to be revealed.AIM To examine the association between single-nucleotide polymorphisms(SNPs)of enzyme genes in the folate metabolite pathway as well as that between GDM-related genes and risk for GDM.METHODS A nested case-control study was conducted with GDM cases(n=412)and healthy controls(n=412).DNA was extracted blood samples and SNPs were genotyped using Agena Bioscience’s MassARRAY gene mass spectrometry system.The associations between different SNPs of genes and the risk for GDM were estimated using logistic regression models.The generalized multi-factor dimensionality reduction(GMDR)method was used to analyze gene-gene and gene-environment interactions using the GMDR 0.9 software.RESULTS The variation allele frequency of melatonin receptor 1B(MTNR1B)rs10830963 was higher in the GDM group than in controls(P<0.05).MTNR1B rs10830963 mutant G was associated with risk for GDM[adjusted odds ratio(aOR):1.43;95%confidence interval(95%CI):1.13-1.80]in the additive model.MTNR1B rs10830963 GG+GC was significantly associated with the risk for GDM(aOR:1.65;95%CI:1.23-2.22)in the dominant model.The two-locus model of MTNR1B rs10830963 and CHEMERIN rs4721 was the best model(P<0.05)for gene-gene interactions in the GMDR results.The high-risk rs10830963×rs4721 type of interaction was a risk factor for GDM(aOR:2.09;95%CI:1.49-2.93).CONCLUSION This study does not find an association between SNPs of folate metabolic enzymes and risk for GDM.The G mutant allele of MTNR1B rs10830963 is identified as a risk factor for GDM in the additive model,and there may be gene-gene interactions between MTNR1B rs10830963 and CHEMERIN rs4721.It is conducive to studying the causes of GDM and provides a new perspective for the precise prevention of this disease.展开更多
BACKGROUND Folate metabolism gene polymorphisms may play an important role in the pathogenesis of autism spectrum disorder(ASD).However,most studies have primarily used single candidate gene typing strategies(such as ...BACKGROUND Folate metabolism gene polymorphisms may play an important role in the pathogenesis of autism spectrum disorder(ASD).However,most studies have primarily used single candidate gene typing strategies(such as targeted polymerase chain reaction technology),and current findings remain inconsistent.AIM To investigate the association of folate metabolism gene polymorphisms with ASD susceptibility and symptom severity among Chinese children.METHODS Whole-exome sequencing(WES)was conducted to systematically screen for coding region variants of key genes in the folate metabolism pathway among children with ASD,focusing on identifying polymorphisms with high mutation frequencies and potential pathogenic effects.A case-control study was then conducted to explore the association of candidate folate metabolism gene polymorphisms with the susceptibility and severity of ASD.RESULTS WES was performed on 70 children with ASD,and the case-control study included 170 children with ASD and 170 healthy controls.WES revealed that 84.3%(59/70)of children with ASD carried potentially pathogenic variants enriched in folate metabolism pathways.MTHFR C677T and MTRR A66G were significantly associated with an increased risk of ASD in both codominant and dominant models(P<0.05).The dominant model of MTRR A66G was also significantly associated with higher scores in the domains of social relations,body and object use,social and adaptive skills,total scores on the Autism Behavior Checklist,as well as emotional reactivity,nonverbal communication,and activity level on the Childhood Autism Rating Scale(P<0.05).CONCLUSION Most children with ASD carry deleterious variants in folate metabolism-related pathways.MTHFR C677T and MTRR A66G mutations are significantly associated with ASD.展开更多
Folic acid(FA)deficiency during pregnancy is a significant risk factor for neural tube defects in infants.Appropriate supplementation with FA has been shown to effectively mitigate the risk of such congenital anomalie...Folic acid(FA)deficiency during pregnancy is a significant risk factor for neural tube defects in infants.Appropriate supplementation with FA has been shown to effectively mitigate the risk of such congenital anomalies.However,genetic polymorphisms related to FA metabolism influence individual variations in FA utilization among pregnant women,highlighting the need for personalized supplementation strategies.This study aimed to explore the impact of genetic variations in FA metabolism-related genes,specifically methylenetetrahydrofolate reductase(MTHFR)and methionine synthase reductase(MTRR),on tailoring FA supplementation during pregnancy.Using fluorescence hybridization sequencing,we analyzed polymorphisms in the MTHFR and MTRR genes among 694 pregnant women,who were divided into an individualized supplementation group and a control group.Pregnancy outcomes were monitored through outpatient visits and telephone follow-ups to evaluate the effect of personalized FA supplementation guided by genetic profiling.Notable differences in genotype frequencies of MTHFR(rs1801133,rs1801131)and MTRR(rs1801394)were observed between pregnant women with and without a heightened risk of FA metabolism disorders(P<0.05).Similarly,allele frequencies of MTHFR(rs1801133)and MTRR(rs1801394)varied significantly among women with different risk profiles(P<0.05).The results demonstrated that the individualized group exhibited significantly lower incidences of birth defects,preterm delivery,spontaneous abortion,premature rupture of membranes,abnormal amniotic fluid,and gestational hypertension compared to the control group(P<0.05).These findings suggested that polymorphisms in MTHFR and MTRR genes were key determinants of FA metabolism and might contribute to adverse pregnancy outcomes in populations with a high prevalence of FA metabolism disorders.Furthermore,integrating genetic screening into FA supplementation protocols enabled more effective prevention of pregnancy complications and improved overall maternal and fetal health outcomes.展开更多
Kawasaki disease(KD)is a systemic vasculitis primarily affecting children,and represents a major cause of acquired heart disease in this population.Although the etiology of KD remains incompletely understood,existing ...Kawasaki disease(KD)is a systemic vasculitis primarily affecting children,and represents a major cause of acquired heart disease in this population.Although the etiology of KD remains incompletely understood,existing genome-wide association studies and genome-wide linkage studies have uncovered various susceptibility genes and their associated chromosomal regions as closely related to the onset and progression of KD.With the rapid advancement of high-throughput DNA sequencing technology,an increasing amount of genomic information pertinent to KD has been discovered,offering new perspectives to investigate the pathogenesis of KD.In particular,genetic polymorphisms play a pivotal role in the immune response,coronary artery lesions,and treatment responsiveness in KD,providing fresh insights into optimizing diagnostic and therapeutic strategies.This article aimed to review and summarize the crucial role of genetic polymorphisms in the pathogenesis of KD,analyze the latest advancements in current research,and discuss the potential applications of gene polymorphism studies in the future diagnosis and treatment of KD.展开更多
BACKGROUND Depression is a disease with a significant global social burden.Single nucleotide polymorphisms(SNPs)are correlated with the development of depression.This study investigates the relationship between polymo...BACKGROUND Depression is a disease with a significant global social burden.Single nucleotide polymorphisms(SNPs)are correlated with the development of depression.This study investigates the relationship between polymorphisms in the GPHN and ATP6V1D gene promoter regions and susceptibility to depression in the Chinese population.AIM To provide new insights into identifying SNPs for predicting depression in the Chinese population.METHODS We conducted a case-control study involving 555 individuals with depression and 509 healthy controls.GPHN rs8020095 and ATP6V1D rs3759755,rs10144417,rs2031564,and rs8016024 in the promoter region were genotyped using nextgeneration sequencing.Dual luciferase reporter genes were employed to assess the transcriptional activity of promoter regions for each SNP genotype,with transcription factors binding to each site predicted using the JASPAR database.RESULTS Compared to healthy controls,the ATP6V1D promoter rs10144417 AG genotype (P = 0.015), rs3759755 AC/CC genotype (P = 0.036), and GPHN gene rs8020095 GA and AA genotypes (GA: P =0.028, GG: P = 0.025) were significantly associated with a lower prevalence of depression. Linked disequilibria werepresent in five SNPs, with the AGATA haplotype frequency in patients significantly lower than in healthy subjects(P = 0.023). Luciferase activity of the rs3759755-A recombinant plasmid was significantly higher than that of thers3759755-C recombinant plasmid (P = 0.026), and the rs8020095-A recombinant plasmid activity was significantlyhigher than that of the rs8020095-G recombinant plasmid (P = 0.001). Transcription factors orthodenticle homeobox2, orthodenticle homeobox 1, forkhead box L1, NK homeobox 3-1, and nuclear factor, interleukin 3 regulateddemonstrated binding affinity with rs3759755A > C and rs8020095A > G.CONCLUSIONThis study demonstrates that SNPs (rs3759755 and rs10144417) in the promoter region of the ATP6V1D and SNP(rs8020095) of GPHN are indeed associated with susceptibility to depression.展开更多
Hepatitis B virus remains a major cause of cirrhosis and hepatocellular carcinoma,with genetic polymorphisms and mutations influencing immune responses and disease progression.Nguyen et al present novel findings on sp...Hepatitis B virus remains a major cause of cirrhosis and hepatocellular carcinoma,with genetic polymorphisms and mutations influencing immune responses and disease progression.Nguyen et al present novel findings on specific human leukocyte antigen(HLA)alleles,including rs2856718 of HLA-DQ and rs3077 and rs9277535 of HLA-DP,which may predispose individuals to cirrhosis and liver cancer,based on multi-clustering analysis.Here,we discuss the feasibility of this approach and identify key areas for further investigation,aiming to offer insights for advancing clinical practice and research in liver disease and related cancers.展开更多
BACKGROUND Nasopharyngeal carcinoma(NPC),exhibiting high incidence in southern China,is linked to genetic and environmental factors.Vitamin D metabolism,involving transport[group-specific component(GC)protein]and acti...BACKGROUND Nasopharyngeal carcinoma(NPC),exhibiting high incidence in southern China,is linked to genetic and environmental factors.Vitamin D metabolism,involving transport[group-specific component(GC)protein]and activation[25-hydroxylase(CYP2R1)enzyme],may influence NPC susceptibility and radiotherapy response.Polymorphisms in GC and CYP2R1 genes affect protein function and serum 25-hydroxyvitamin D[25(OH)D]levels,and are implicated in other cancers.However,their role in NPC-particularly in high-risk Han Chinese populations-and interaction with vitamin D status remains unclear.This case control study(360 NPC patients,550 controls)investigates these relationships to inform prevention and personalized therapy.AIM To investigate the association between vitamin D binding protein(GC)and CYP2R1 gene polymorphisms with susceptibility to NPC and radiotherapy response.METHODS A case control study design was adopted,and 360 patients with NPC and 550 healthy controls were included.TaqMan method was used to perform genotyping on GC gene loci rs4588,rs7041,and CYP2R1 gene loci rs10741657,rs12794714.Serum 25(OH)D levels were detected,and the relationship between gene polymorphisms and NPC risk and radiotherapy response was analyzed.RESULTS The GC gene rs4588 TT genotype was significantly associated with the risk of NPC in both the codominant model[odds ratio(OR)=1.68,95%CI:1.15-2.45,P=0.007]and the recessive model(OR=1.56,95%CI:1.02-2.38,P=0.039).The association between the rs4588 TT genotype and the risk of NPC was more significant in the male subgroup(OR=1.87,95%CI:1.11-3.15,P=0.019)and the squamous cell carcinoma subgroup(OR=1.89,95%CI:1.19-3.00,P=0.007).The serum 25(OH)D level of the rs7041 AA genotype carriers was significantly lower than that of the CC genotype(P<0.001).The CYP2R1 gene rs10741657 AA genotype was associated with higher serum 25(OH)D levels(P=0.003).The rs12794714 AA genotype was associated with radiotherapy resistance(OR=1.76,95%CI:1.18-2.63,P=0.005).Stratified analysis showed that the association between rs4588 and rs12794714 was significant only in the subgroup with higher 25(OH)D levels.CONCLUSION GC and CYP2R1 genes polymorphisms are associated with NPC susceptibility and radiotherapy response,and this association may be affected by serum 25(OH)D levels.This study provides a new idea for the prevention and individualized treatment in NPC.展开更多
Fluoropyrimidines(FP),including 5-fluorouracil and its prodrug capecitabine,are commonly employed in treating various solid tumors.Nonetheless,their use is frequently constrained by severe toxicities in 20%-30%of pati...Fluoropyrimidines(FP),including 5-fluorouracil and its prodrug capecitabine,are commonly employed in treating various solid tumors.Nonetheless,their use is frequently constrained by severe toxicities in 20%-30%of patients.Pharmacogenetic testing for dihydropyrimidine dehydrogenase(DPYD)deficiency,based on DPYD polymorphisms,has notably decreased severe adverse events,improving the safety of FP therapy.A recent D'Amato et al study evaluated the prevalence of DPYD polymorphisms and their effect on FP tolerability among Italian patients with gastrointestinal cancers.Although this study provided important insights into the significance of DPYD testing,its retrospective nature,inconsistency in testing DPYD variants,and lack of consideration for socioeconomic and confounding factors showed considerable limitations.Expanding the screening to include DPYD variants,addressing confounding biases through robust statistical analyses,and implementing prospective studies are critical next steps to strengthen the clinical evidence.Furthermore,the absence of a comprehensive cost-effectiveness analysis highlights the need for further financial assessments to advocate for broader implementation.We emphasized integrating DPYD-guided dosing,pre-treatment genetic counseling,and standardized testing procedures into clinical practice to improve patient outcomes and minimize treatment-related toxicities.展开更多
BACKGROUND Coronary heart disease(CHD)is a prominent cause of mortality and disability worldwide.Like most complex diseases,the risk of CHD in individuals is regulated by the interaction between genetic factors and li...BACKGROUND Coronary heart disease(CHD)is a prominent cause of mortality and disability worldwide.Like most complex diseases,the risk of CHD in individuals is regulated by the interaction between genetic factors and lifestyle.APOE and SLCO1B1 genetic polymorphisms and LPA KIV-2 copy number variation may influence the development and progression of CHD.Clarifying gene polymor-phisms can guide clinical precision and prevention,thereby improving treatment outcomes.AIM To investigate the influence of APOE and SLCO1B1 gene polymorphisms,as well as LPA KIV-2 copy number variation on CHD in the Teochew population.METHODS A total of 324 patients with CHD and 143 control participants were involved in this study.Single nucleotide polymorphisms rs429358 and rs7412 in the APOE gene,and rs2306283 and rs4149056 in the SLCO1B1 gene were analyzed via high-resolution melting curve analysis.Additionally,PCR was performed to detect KIV-2 copy number variations.Clinical risk factors and potential effects on CHD patients were subsequently assessed.RESULTS In the CHD group,the frequencies of APOE alleleε2,ε3,ε4 were 8.02%,82.97%,and 9.10%,respectively.Compared to the control groups(13.29%,79.37%,and 7.34%,respectively),theε2 allele frequency showed a significant difference(8.02%vs 13.29%,P=0.012).SLCO1B1 allele frequencies in the CHD group were not significantly different from those in the control group(*1a:26.69%vs 25.52%,*1b:61.17%vs 65.38%,*5:0.15%vs 0.35%,*15:11.83%vs 8.74%).The number of copies of the KIV-2 gene was significantly lower in the CHD group when compared to controls(23.35±8.78 vs 27.21±9.48;P<0.01).Logistic regression analysis revealed that sex,age,hypertension,diabetes,smoking,theε2 allele and KIV-2 copy number were factors influencing the presence of CHD.CONCLUSION In the Teochew population,the APOEε2 allele and a higher KIV-2 copy number were associated with a reduced risk of CHD.In contrast,the APOEε4 allele and SLCO1B1 gene were not associated with CHD.展开更多
文摘[Objective] To explore the polymorphism of the 3′ flank region of equine IGF-Ⅰ gene. [Method] The 3′ flank region sequences of IGF-Ⅰ gene were amplified from genomic DNA of 270 horses, which included 4 types of Mongolian horse, Sanhe horse and Thoroughbred, and then analyzed by PCR-SSCP. [Result] Three genotypes (AA, BB and AB) were detected by PCR-SSCP and the distribution of genotypes of all research objects except Xinihe horse and Baerhu horse were in line with the "Hardy-Weinberg Law". [Conclusion] There was a polymorphic locus in the 3′ flank region of IGF-Ⅰ gene, which might affect the equine growth and development mechanism. The study is of important theoretical and practical significance to improve the performance and to develop equine industry.
文摘By employing different gel components and electrophoresis conditions, the PCR-SSCP(polymerase chain reaction-single-stranded conformation polymorphism) method was used to detect the polymorphism(CCC or CGC ) of codon 72 in exon 4 of p53 gene. The results
文摘Polymorphisms of porcine ob exon 1 and exon 2 among different breeds including Landrace, Duroc, Min pig, Yorkshire pig, double-muscled Yorkshire, Sanjiang pig, wild boar and cross bred pig were analyzed by PCR-SSCP in the current study. Three pairs of primers according to the ob cDNA sequence obtained from GenBank database were designed to amplify the first two exons, which were then genotyped by SSCP. The T to C transversion was found in exon 2, which resulted in 3 genotypes named AA, AB and BB, respectively in these different porcine breeds. There was only genotype of BB in the Min pig, while no allele B was detected in double-muscled Yorkshire, and the 3 genotypes all existed in other breeds. There was significant difference on the genotype frequencies in various breeds. There was a trend that the frequency of allele A was positively associated with muscle ratio distribution on the one hand, and on the other hand, it was linked to the selected direction. So the allele A could be used as a selective marker of high muscle ratio in pig breeding.
文摘The rRNA genetic locus is found in all prokaryotic organisms, and is highly conservative, although its relatively stable variations are found frequently in different bacteria. The utility of this locus as a taxonomic and phylogenetic tool has been reported widely. This study, aimed at 16S rRNA gene (16S rDNA) and with the help of biomolecular methods, attempted to achieve the goal of rapid identification of common pathogens. In this study, 333 clinical isolated pathogenic bacteria were collected. Two pairs of primers were chosen and labeled with different fluorescent dyes and then used to amplify the genomic DNA extracted from bacteria. The PCR products were then detected by capillary electrophoresis-single strand conformation polymorphism (CE-SSCP). In order to pursue higher resolution and peak-separation effect, a high efficient separating medium, liner polyacrylamidedel (LPA), was put to use in this study. Finally, every bacteria colony generated distinct patterns from each other, which were easily to be used for identification. These results indicated that PCR-CE-SSCP was a rapid identification method for bacterial identification, with the aspects of high efficiency and high precision. Compared with traditional method, this technology is of great utility for clinical use especially for its high sensitivity.
文摘Objective: To study the relationship between the polymorphism of drug resistant gene rpoB and drug resistance against rifampicin(RFP) of M. tuberculosis L-forms, and to evaluate its clinical application. Methods: A total of 52 clinical isolated strains of M. tuberculosis L-forms were collected. rpoB gene polymorphism was analyzed by polymerase chain reaction and single-strand conformation polymorphism (PCR-SSCP) and conventional antimicrobial susceptibility test (AST). Their results were compared. Results: AST results showed that 38 of 52 clinical isolated strains were drug resistance (73.08％),while PCR-SSCP indicated 65.38％ (32/52) rpoB gene polymorphism. There was no statistic significance(χ2= 2.4914) between the 2 methods. Conclusion:Combined the application of PCR-SSCP with AST in detecting rpoB drug resistant gene polymorphism of M. tuberculosis L-form from pneumoconiosis patients with tuberculosis may have advantages at earlier diagnosis and guidance of clinical medications.
基金Supported by The National Natural Science Foundation of China,No.82350127 and No.82241013the Shanghai Natural Science Foundation,No.20ZR1411600+2 种基金the Shanghai Shenkang Hospital Development Center,No.SHDC2020CR4039the Bethune Ethicon Excellent Surgery Foundation,No.CESS2021TC04Xuhui District Medical Research Project of Shanghai,No.SHXH201805.
文摘BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis through binding to dif-ferent ligands.AIM To evaluate the correlation between single nucleotide polymorphisms(SNPs)of ACVR1C and susceptibility to esophageal squamous cell carcinoma(ESCC)in Chinese Han population.METHODS In this hospital-based cohort study,1043 ESCC patients and 1143 healthy controls were enrolled.Five SNPs(rs4664229,rs4556933,rs77886248,rs77263459,rs6734630)of ACVR1C were assessed by the ligation detection reaction method.Hardy-Weinberg equilibrium test,genetic model analysis,stratified analysis,linkage disequi-librium test,and haplotype analysis were conducted.RESULTS Participants carrying ACVR1C rs4556933 GA mutant had significantly decreased risk of ESCC,and those with rs77886248 TA mutant were related with higher risk,especially in older male smokers.In the haplotype analysis,ACVR1C Trs4664229Ars4556933Trs77886248Crs77263459Ars6734630 increased risk of ESCC,while Trs4664229Grs4556933Trs77886248Crs77263459Ars6734630 was associated with lower susceptibility to ESCC.CONCLUSION ACVR1C rs4556933 and rs77886248 SNPs were associated with the susceptibility to ESCC,which could provide a potential target for early diagnosis and treatment of ESCC in Chinese Han population.
基金funded by the National Natural Science Foundation of China(grant no.32270238 and 31870311).
文摘Subtropical evergreen broad-leaved trees are usually vulnerable to freezing stress,while hexaploid wild Camellia oleifera shows strong freezing tolerance.As a valuable genetic resource of woody oil crop C.oleifera,wild C.oleifera can serve as a case for studying the molecular bases of adaptive evolution to freezing stress.Here,47 wild C.oleifera from 11 natural distribution sites in China and 4 relative species of C.oleifera were selected for genome sequencing.“Min Temperature of Coldest Month”(BIO6)had the highest comprehensive contribution to wild C.oleifera distribution.The population genetic structure of wild C.oleifera could be divided into two groups:in cold winter(BIO6≤0℃)and warm winter(BIO6>0℃)areas.Wild C.oleifera in cold winter areas might have experienced stronger selection pressures and population bottlenecks with lower N_(e) than those in warm winter areas.155 singlenucleotide polymorphisms(SNPs)were significantly correlated with the key bioclimatic variables(106 SNPs significantly correlated with BIO6).Twenty key SNPs and 15 key copy number variation regions(CNVRs)were found with genotype differentiation>50%between the two groups of wild C.oleifera.Key SNPs in cis-regulatory elements might affect the expression of key genes associated with freezing tolerance,and they were also found within a CNVR suggesting interactions between them.Some key CNVRs in the exon regions were closely related to the differentially expressed genes under freezing stress.The findings suggest that rich SNPs and CNVRs in polyploid trees may contribute to the adaptive evolution to freezing stress.
文摘BACKGROUND Fluoropyrimidines are metabolized in the liver by the enzyme dihydropyrimidine dehydrogenase(DPD),encoded by the DPYD gene.About 7%of the European population is a carrier of DPYD gene polymorphisms associated with reduced DPD enzyme activity.AIM To assess the prevalence of DPYD polymorphisms and their impact on fluoropyrimidine tolerability in Italian patients with gastrointestinal malignancies.METHODS A total of 300 consecutive patients with a diagnosis of gastrointestinal malignancy and treated with a fluoropyrimidine-based regimen were included in the analysis and divided into two cohorts:(1)149 patients who started fluoropyrimidines after DPYD testing;and(2)151 patients treated without DPYD testing.Among the patients in cohort A,15%tested only the DPYD2A polymorphism,19%tested four polymorphisms(DPYD2A,HapB3,c.2846A>T,and DPYD13),and 66%tested five polymorphisms including DPYD6.RESULTS Overall,14.8%of patients were found to be carriers of a DPYD variant,the most common being DPYD6(12.1%).Patients in cohort A reported≥G3 toxicities(P=0.00098),particularly fewer nonhematological toxicities(P=0.0028)compared with cohort B,whereas there was no statistically significant difference between the two cohorts in hematological toxicities(P=0.6944).Significantly fewer chemotherapy dose reductions(P=0.00002)were observed in cohort A compared to cohort B,whereas there was no statistically significant differences in chemotherapy delay.CONCLUSION Although this study had a limited sample size,it provides additional information on the prevalence of DPYD polymorphisms in the Italian population and highlights the role of pharmacogenetic testing to prevent severe toxicity.
基金financially supported by the National Natural Science Foundation of China(NSFC,Nos.22075168,21701105,21871167&91961201)Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering(No.2022SX-FR003)。
文摘In our work,polymorphism strategy has been successfully applied to tune up chromism and luminescence properties of viologen-based materials.Two polymorphs of viologen-based complexes ofα-CdBr_(2)(PHSQ)_(2)(H_(2)O)_(2)(1)andβ-CdBr_(2)(PHSQ)_(2)(H_(2)O)_(2)(2)(PHSQ=N-(4-sulfophenyl)-4,4-bipyridinium)were synthesized by changing the solvent.They can both respond to UV light and electricity in the manner of chromism visible to the naked eye and the coloration states have good reversibility,through which an inkless erasable printing model has been established.But the coloration contrast of 1 is higher compared to 2.Meanwhile,they both exhibit photoluminescence properties and the intensity of 1 is twice that of 2,which is accompanied by photoquenching upon continuous UV light irradiation.The only divergence of disordered/ordered O atoms in the two crystalline compounds leads to significantly different chromic and luminescent properties.Further explorations simultaneously demonstrate that the different chromic performance between 1 and 2 should attribute to the alteration of stimulus-induced(light/electricity)electron transfer channels caused by the ordered/disordered O atoms in the complexes,which is achieved through C-H···O and O-H···O interactions to change crystal arrangement and structural rigidity,thus affect luminescent properties.
基金National Key Research and Development Program for Young scientists,Grant/Award Number:2021YFF0703200National Natural Foundation Joint Fund for Regional Innovation and Development,Grant/Award Number:U21A20194+1 种基金National Natural Science Foundation of China,Grant/Award Number:32170540National Key Research and Development Program,Grant/Award Number:2022YFF0711005。
文摘Chinese hamster with Chinese characteristics is used in experiments,and it is of great value in the field of medical biology research.However,at present,there is no high-efficiency method for evaluating the genetic quality of Chinese hamsters.Here,we developed a novel Chinese hamster genetic quality detection system using single-nucleotide polymorphism(SNP)markers.To find SNP loci,we conducted whole genome sequencing on 24 Chinese hamsters.Then,we employed an SNP locus screening criterion that we set up previously and initially screened 214 SNP loci with wide genome distribution and high polymorphism level.Subsequently,we developed the SNP detection system using a multitarget region capture technique based on second-generation sequencing,and a 55 SNP panel for genetic evaluation of Chinese hamster populations was developed.PopGen.32.analysis results showed that the average effective allele number,Shannon index,observed heterozygosity,expected heterozygosity,average heterozygosity,polymorphism information,and other genetic parameters of Chinese hamster population A were higher than those in population B.Using scientific screening and optimization,we successfully developed a novel Chinese hamster SNP genetic detection system that can efficiently and accurately analyze the genetic quality of the Chinese hamster population.
文摘Methylenetetrahydrofolate reductase(MTHFR)is a key enzyme in folate metabolism.Its genetic polymorphisms affect the metabolism of methyl donors,including folate and betaine,and are consequently associated with the development of various chronic diseases such as stroke and neoplasms.Methods This umbrella review,covering the period from 2006 to 2025,searched PubMed,Embase,Web of Science,Medline,CNKI,WanFang,and Cochrane Library databases for published systematic reviews and meta-analyses of polymorphisms relating to the MTHFR C677T and A1298C gene polymorphisms and various chronic diseases.Subsequently,this study assessed methodological quality with AMSTAR-2,while the strength of evidence for each outcome was graded according to the GRADE and the credibility evaluation.This umbrella review included 39 studies related to 8 diseases classified according to the ICD-10 classification.Results Overall,C677T exhibited a positive correlation with depression(allele:OR=1.18,95%CI:1.13-1.24;dominant:OR=1.16,95%CI:1.09-1.23;recessive:OR=1.42,95%CI:1.30-1.56;homozygote:OR=1.48,95%CI:1.34-1.63),and polycystic ovary syndrome(allele:OR=1.35,95%CI:1.24-1.46;dominant:OR=1.46,95%CI:1.30-1.64;recessive:OR=1.39,95%CI:1.19-1.62;homozygote:OR=1.63,95%CI:1.38-1.93),and exhibited a negative correlation with oral cancer(allele:OR=0.24,95%CI:0.22-0.26;dominant:OR=0.14,95%CI:0.12-0.16;recessive:OR=0.31,95%CI:0.28-0.35;homozygote:OR=0.14,95%CI:0.12-0.16).A1298C was positively associated with polycystic ovary syndrome in four models(allele:OR=1.93,95%CI:1.67-2.21;dominant:OR=1.93,95%CI:1.64-2.27;recessive:OR=3.72,95%CI:2.47-5.61;homozygote:OR=4.38,95%CI:2.90-6.62).Conclusion The MTHFR C677T and A1298C gene polymorphisms demonstrated significant associations with non-communicable diseases,thereby contributing to the advancement of precision medicine.
基金Supported by the National Key Research and Development Program of China,No.2021YFC2700700 and No.2021YFC2700704Capital’s Funds for Health Improvement and Research(CFH)in People’s Republic of China,No.2020-1-5112.
文摘BACKGROUND There are conflicting results on the potential correlation between folic acid and gestational diabetes mellitus(GDM),and the correlation between genetic factors related to folic acid metabolism pathways and GDM remains to be revealed.AIM To examine the association between single-nucleotide polymorphisms(SNPs)of enzyme genes in the folate metabolite pathway as well as that between GDM-related genes and risk for GDM.METHODS A nested case-control study was conducted with GDM cases(n=412)and healthy controls(n=412).DNA was extracted blood samples and SNPs were genotyped using Agena Bioscience’s MassARRAY gene mass spectrometry system.The associations between different SNPs of genes and the risk for GDM were estimated using logistic regression models.The generalized multi-factor dimensionality reduction(GMDR)method was used to analyze gene-gene and gene-environment interactions using the GMDR 0.9 software.RESULTS The variation allele frequency of melatonin receptor 1B(MTNR1B)rs10830963 was higher in the GDM group than in controls(P<0.05).MTNR1B rs10830963 mutant G was associated with risk for GDM[adjusted odds ratio(aOR):1.43;95%confidence interval(95%CI):1.13-1.80]in the additive model.MTNR1B rs10830963 GG+GC was significantly associated with the risk for GDM(aOR:1.65;95%CI:1.23-2.22)in the dominant model.The two-locus model of MTNR1B rs10830963 and CHEMERIN rs4721 was the best model(P<0.05)for gene-gene interactions in the GMDR results.The high-risk rs10830963×rs4721 type of interaction was a risk factor for GDM(aOR:2.09;95%CI:1.49-2.93).CONCLUSION This study does not find an association between SNPs of folate metabolic enzymes and risk for GDM.The G mutant allele of MTNR1B rs10830963 is identified as a risk factor for GDM in the additive model,and there may be gene-gene interactions between MTNR1B rs10830963 and CHEMERIN rs4721.It is conducive to studying the causes of GDM and provides a new perspective for the precise prevention of this disease.
基金Supported by the National Key Research and Development Program of China,No.2024YFC2707801the Science and Technology Innovation Commission of Shenzhen,No.JCYJ20230807143800002.
文摘BACKGROUND Folate metabolism gene polymorphisms may play an important role in the pathogenesis of autism spectrum disorder(ASD).However,most studies have primarily used single candidate gene typing strategies(such as targeted polymerase chain reaction technology),and current findings remain inconsistent.AIM To investigate the association of folate metabolism gene polymorphisms with ASD susceptibility and symptom severity among Chinese children.METHODS Whole-exome sequencing(WES)was conducted to systematically screen for coding region variants of key genes in the folate metabolism pathway among children with ASD,focusing on identifying polymorphisms with high mutation frequencies and potential pathogenic effects.A case-control study was then conducted to explore the association of candidate folate metabolism gene polymorphisms with the susceptibility and severity of ASD.RESULTS WES was performed on 70 children with ASD,and the case-control study included 170 children with ASD and 170 healthy controls.WES revealed that 84.3%(59/70)of children with ASD carried potentially pathogenic variants enriched in folate metabolism pathways.MTHFR C677T and MTRR A66G were significantly associated with an increased risk of ASD in both codominant and dominant models(P<0.05).The dominant model of MTRR A66G was also significantly associated with higher scores in the domains of social relations,body and object use,social and adaptive skills,total scores on the Autism Behavior Checklist,as well as emotional reactivity,nonverbal communication,and activity level on the Childhood Autism Rating Scale(P<0.05).CONCLUSION Most children with ASD carry deleterious variants in folate metabolism-related pathways.MTHFR C677T and MTRR A66G mutations are significantly associated with ASD.
基金Key Laboratory Construction and Operation Project of Qinzhou Science and Technology Bureau(Grant No.20242422).
文摘Folic acid(FA)deficiency during pregnancy is a significant risk factor for neural tube defects in infants.Appropriate supplementation with FA has been shown to effectively mitigate the risk of such congenital anomalies.However,genetic polymorphisms related to FA metabolism influence individual variations in FA utilization among pregnant women,highlighting the need for personalized supplementation strategies.This study aimed to explore the impact of genetic variations in FA metabolism-related genes,specifically methylenetetrahydrofolate reductase(MTHFR)and methionine synthase reductase(MTRR),on tailoring FA supplementation during pregnancy.Using fluorescence hybridization sequencing,we analyzed polymorphisms in the MTHFR and MTRR genes among 694 pregnant women,who were divided into an individualized supplementation group and a control group.Pregnancy outcomes were monitored through outpatient visits and telephone follow-ups to evaluate the effect of personalized FA supplementation guided by genetic profiling.Notable differences in genotype frequencies of MTHFR(rs1801133,rs1801131)and MTRR(rs1801394)were observed between pregnant women with and without a heightened risk of FA metabolism disorders(P<0.05).Similarly,allele frequencies of MTHFR(rs1801133)and MTRR(rs1801394)varied significantly among women with different risk profiles(P<0.05).The results demonstrated that the individualized group exhibited significantly lower incidences of birth defects,preterm delivery,spontaneous abortion,premature rupture of membranes,abnormal amniotic fluid,and gestational hypertension compared to the control group(P<0.05).These findings suggested that polymorphisms in MTHFR and MTRR genes were key determinants of FA metabolism and might contribute to adverse pregnancy outcomes in populations with a high prevalence of FA metabolism disorders.Furthermore,integrating genetic screening into FA supplementation protocols enabled more effective prevention of pregnancy complications and improved overall maternal and fetal health outcomes.
文摘Kawasaki disease(KD)is a systemic vasculitis primarily affecting children,and represents a major cause of acquired heart disease in this population.Although the etiology of KD remains incompletely understood,existing genome-wide association studies and genome-wide linkage studies have uncovered various susceptibility genes and their associated chromosomal regions as closely related to the onset and progression of KD.With the rapid advancement of high-throughput DNA sequencing technology,an increasing amount of genomic information pertinent to KD has been discovered,offering new perspectives to investigate the pathogenesis of KD.In particular,genetic polymorphisms play a pivotal role in the immune response,coronary artery lesions,and treatment responsiveness in KD,providing fresh insights into optimizing diagnostic and therapeutic strategies.This article aimed to review and summarize the crucial role of genetic polymorphisms in the pathogenesis of KD,analyze the latest advancements in current research,and discuss the potential applications of gene polymorphism studies in the future diagnosis and treatment of KD.
基金Supported by the Natural Science Foundation of Sichuan,China,No.2022NSFSC0778Research Project Foundation of Sichuan Applied Psychology Research Center,No.CSXL-24202+1 种基金Foundation of Sichuan Clinical Research Center for Geriatrics,No.24LHLNYX1-04 and No.24LHLNYX1-06and the Key Laboratory Foundation for Development and Regeneration of Sichuan Province,No.24LHFYSZ1-25.
文摘BACKGROUND Depression is a disease with a significant global social burden.Single nucleotide polymorphisms(SNPs)are correlated with the development of depression.This study investigates the relationship between polymorphisms in the GPHN and ATP6V1D gene promoter regions and susceptibility to depression in the Chinese population.AIM To provide new insights into identifying SNPs for predicting depression in the Chinese population.METHODS We conducted a case-control study involving 555 individuals with depression and 509 healthy controls.GPHN rs8020095 and ATP6V1D rs3759755,rs10144417,rs2031564,and rs8016024 in the promoter region were genotyped using nextgeneration sequencing.Dual luciferase reporter genes were employed to assess the transcriptional activity of promoter regions for each SNP genotype,with transcription factors binding to each site predicted using the JASPAR database.RESULTS Compared to healthy controls,the ATP6V1D promoter rs10144417 AG genotype (P = 0.015), rs3759755 AC/CC genotype (P = 0.036), and GPHN gene rs8020095 GA and AA genotypes (GA: P =0.028, GG: P = 0.025) were significantly associated with a lower prevalence of depression. Linked disequilibria werepresent in five SNPs, with the AGATA haplotype frequency in patients significantly lower than in healthy subjects(P = 0.023). Luciferase activity of the rs3759755-A recombinant plasmid was significantly higher than that of thers3759755-C recombinant plasmid (P = 0.026), and the rs8020095-A recombinant plasmid activity was significantlyhigher than that of the rs8020095-G recombinant plasmid (P = 0.001). Transcription factors orthodenticle homeobox2, orthodenticle homeobox 1, forkhead box L1, NK homeobox 3-1, and nuclear factor, interleukin 3 regulateddemonstrated binding affinity with rs3759755A > C and rs8020095A > G.CONCLUSIONThis study demonstrates that SNPs (rs3759755 and rs10144417) in the promoter region of the ATP6V1D and SNP(rs8020095) of GPHN are indeed associated with susceptibility to depression.
基金Supported by National Natural Science Foundation of China,No.32270768,No.82273970,No.32070726,and No.82370715National Key R&D Program of China,No.2023YFC2507904the Innovation Group Project of Hubei Province,No.2023AFA026.
文摘Hepatitis B virus remains a major cause of cirrhosis and hepatocellular carcinoma,with genetic polymorphisms and mutations influencing immune responses and disease progression.Nguyen et al present novel findings on specific human leukocyte antigen(HLA)alleles,including rs2856718 of HLA-DQ and rs3077 and rs9277535 of HLA-DP,which may predispose individuals to cirrhosis and liver cancer,based on multi-clustering analysis.Here,we discuss the feasibility of this approach and identify key areas for further investigation,aiming to offer insights for advancing clinical practice and research in liver disease and related cancers.
文摘BACKGROUND Nasopharyngeal carcinoma(NPC),exhibiting high incidence in southern China,is linked to genetic and environmental factors.Vitamin D metabolism,involving transport[group-specific component(GC)protein]and activation[25-hydroxylase(CYP2R1)enzyme],may influence NPC susceptibility and radiotherapy response.Polymorphisms in GC and CYP2R1 genes affect protein function and serum 25-hydroxyvitamin D[25(OH)D]levels,and are implicated in other cancers.However,their role in NPC-particularly in high-risk Han Chinese populations-and interaction with vitamin D status remains unclear.This case control study(360 NPC patients,550 controls)investigates these relationships to inform prevention and personalized therapy.AIM To investigate the association between vitamin D binding protein(GC)and CYP2R1 gene polymorphisms with susceptibility to NPC and radiotherapy response.METHODS A case control study design was adopted,and 360 patients with NPC and 550 healthy controls were included.TaqMan method was used to perform genotyping on GC gene loci rs4588,rs7041,and CYP2R1 gene loci rs10741657,rs12794714.Serum 25(OH)D levels were detected,and the relationship between gene polymorphisms and NPC risk and radiotherapy response was analyzed.RESULTS The GC gene rs4588 TT genotype was significantly associated with the risk of NPC in both the codominant model[odds ratio(OR)=1.68,95%CI:1.15-2.45,P=0.007]and the recessive model(OR=1.56,95%CI:1.02-2.38,P=0.039).The association between the rs4588 TT genotype and the risk of NPC was more significant in the male subgroup(OR=1.87,95%CI:1.11-3.15,P=0.019)and the squamous cell carcinoma subgroup(OR=1.89,95%CI:1.19-3.00,P=0.007).The serum 25(OH)D level of the rs7041 AA genotype carriers was significantly lower than that of the CC genotype(P<0.001).The CYP2R1 gene rs10741657 AA genotype was associated with higher serum 25(OH)D levels(P=0.003).The rs12794714 AA genotype was associated with radiotherapy resistance(OR=1.76,95%CI:1.18-2.63,P=0.005).Stratified analysis showed that the association between rs4588 and rs12794714 was significant only in the subgroup with higher 25(OH)D levels.CONCLUSION GC and CYP2R1 genes polymorphisms are associated with NPC susceptibility and radiotherapy response,and this association may be affected by serum 25(OH)D levels.This study provides a new idea for the prevention and individualized treatment in NPC.
文摘Fluoropyrimidines(FP),including 5-fluorouracil and its prodrug capecitabine,are commonly employed in treating various solid tumors.Nonetheless,their use is frequently constrained by severe toxicities in 20%-30%of patients.Pharmacogenetic testing for dihydropyrimidine dehydrogenase(DPYD)deficiency,based on DPYD polymorphisms,has notably decreased severe adverse events,improving the safety of FP therapy.A recent D'Amato et al study evaluated the prevalence of DPYD polymorphisms and their effect on FP tolerability among Italian patients with gastrointestinal cancers.Although this study provided important insights into the significance of DPYD testing,its retrospective nature,inconsistency in testing DPYD variants,and lack of consideration for socioeconomic and confounding factors showed considerable limitations.Expanding the screening to include DPYD variants,addressing confounding biases through robust statistical analyses,and implementing prospective studies are critical next steps to strengthen the clinical evidence.Furthermore,the absence of a comprehensive cost-effectiveness analysis highlights the need for further financial assessments to advocate for broader implementation.We emphasized integrating DPYD-guided dosing,pre-treatment genetic counseling,and standardized testing procedures into clinical practice to improve patient outcomes and minimize treatment-related toxicities.
基金Supported by Special Research Plan 2023 of Chaozhou,No.202303GY05。
文摘BACKGROUND Coronary heart disease(CHD)is a prominent cause of mortality and disability worldwide.Like most complex diseases,the risk of CHD in individuals is regulated by the interaction between genetic factors and lifestyle.APOE and SLCO1B1 genetic polymorphisms and LPA KIV-2 copy number variation may influence the development and progression of CHD.Clarifying gene polymor-phisms can guide clinical precision and prevention,thereby improving treatment outcomes.AIM To investigate the influence of APOE and SLCO1B1 gene polymorphisms,as well as LPA KIV-2 copy number variation on CHD in the Teochew population.METHODS A total of 324 patients with CHD and 143 control participants were involved in this study.Single nucleotide polymorphisms rs429358 and rs7412 in the APOE gene,and rs2306283 and rs4149056 in the SLCO1B1 gene were analyzed via high-resolution melting curve analysis.Additionally,PCR was performed to detect KIV-2 copy number variations.Clinical risk factors and potential effects on CHD patients were subsequently assessed.RESULTS In the CHD group,the frequencies of APOE alleleε2,ε3,ε4 were 8.02%,82.97%,and 9.10%,respectively.Compared to the control groups(13.29%,79.37%,and 7.34%,respectively),theε2 allele frequency showed a significant difference(8.02%vs 13.29%,P=0.012).SLCO1B1 allele frequencies in the CHD group were not significantly different from those in the control group(*1a:26.69%vs 25.52%,*1b:61.17%vs 65.38%,*5:0.15%vs 0.35%,*15:11.83%vs 8.74%).The number of copies of the KIV-2 gene was significantly lower in the CHD group when compared to controls(23.35±8.78 vs 27.21±9.48;P<0.01).Logistic regression analysis revealed that sex,age,hypertension,diabetes,smoking,theε2 allele and KIV-2 copy number were factors influencing the presence of CHD.CONCLUSION In the Teochew population,the APOEε2 allele and a higher KIV-2 copy number were associated with a reduced risk of CHD.In contrast,the APOEε4 allele and SLCO1B1 gene were not associated with CHD.
