With completion of the Populus genome sequencing project and the availability of many expressed sequence tags （ESTs） databases in forest trees, attention is now rapidly shifting towards the study of individual genet...With completion of the Populus genome sequencing project and the availability of many expressed sequence tags （ESTs） databases in forest trees, attention is now rapidly shifting towards the study of individual genetic variation in natural populations. The most abundant form of genetic variation in many eukaryotic species is represented by single nucleotide polymorphisms （SNPs）, which can account for heritable inter-individual differences in complex phenotypes. Unlike humans, the linkage disequilibrium （LD） rapidly decays within candidate genes in forest trees. Thus, SNPs-based candidate gene association studies are considered to be a most effective approach to dissect the complex quantitative traits in forest trees. The present study demonstrates that LD mapping can be used to identify alleles associated with quantitative traits and suggests that this new approach could be particularly useful for performing breeding programs in forest trees. In this review, we will describe the fundamentals, patterns of SNPs distribution and frequency, summarize recent advances in SNPs discovery and LD and comment on the application of LD in the dissection of complex quantitative traits in forest tress. We also put forward the outlook for future SNPs-based association analysis of quantitative traits in forest trees.展开更多
Background: More and more chronic kidney disease (CKD) patients are accompanied with hyperuricaemia. As is known, hyperuricaemia is an independent hazard of both cardiovascular diseases (CVD) and chronic kidney diseas...Background: More and more chronic kidney disease (CKD) patients are accompanied with hyperuricaemia. As is known, hyperuricaemia is an independent hazard of both cardiovascular diseases (CVD) and chronic kidney diseases. We aim at identifying Single Nucleotide Polymorphism (SNP) difference of hURAT1 (rs7932775) and ABCG2 (rs3825016) on CKD patient with hyperuricemia and/or gout. Methods: All forty-two CKD patients were divided into two groups: hyperuricemia, and control group. 24 hours urine sample and serum were prepared for testing biochemistry parameters. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method is used to analyze hURAT1 and ABCG2 single nucleotide polymorphisms in different groups. Results: 17 patients have CT SNP of hURAT1 (rs7932775) and 13 patients have CT SNP of ABCG2 (rs3825016) in hyperuricemia group, while only 5 persons and 6 persons have the same mutations in control group respectively. 7 patients have CT SNP of both hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group, while only 2 persons have the same mutations in control group. CT mutation rates of hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group were 60.7% (17/28) and 50% (13/28) respectively, higher than that of control group (35.7% (5/14) and 42.8% (6/14)). What is more, Double SNP mutations in both hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group were 25% (7/28), higher than that of control group (14.2%, 2/14). Conclusion: There are higher mutation rates of CT SNP in hURAT1 (rs7932775) and/or ABCG2 (rs3825016) in hyperuricemia group. We can conclude that hyperuricemia is a high risk factor in progress of CKD, which is necessary to take measures of decreasing serum uric acid to delay CKD progress.展开更多
Nucleotide diversity (pi) and linkage disequilibrium (LD) analysis based on SNP marker could provide a sound basis for choosing an association analysis method. Japanese larch (Larix kaempferi) is an important timber c...Nucleotide diversity (pi) and linkage disequilibrium (LD) analysis based on SNP marker could provide a sound basis for choosing an association analysis method. Japanese larch (Larix kaempferi) is an important timber coniferous tree species for pulping and papermaking, but its high lignin content has significantly restricted it application potential. In this study, the LACCASE gene, that plays an important regulatory role for lignin biosynthesis, was selected as research target. The full-length cDNA and genomic sequences of the encoding LkLAC8 gene were isolated from the LACCASE expressed sequence tags of the Japanese larch transcriptome database using the rapid amplification of cDNA ends-polymerase chain reaction (RACE-PCR). The cDNA was determined to be 1940 bp, with an open reading frame (ORF, 1734 bp) that encoded a protein of 577 AA. This protein contains four highly specific Cu2+ binding sites and 11 glycosylation sites, thus belonging to the LACCASE family. The deduced protein sequence shared an 89% identity with the PtaLAC from Pinus taeda. A real-time PCR analysis showed that the LkLAC8 transcript was expressed predominantly in mature xylem, with moderate levels in the immature xylem, cambium and mature leaves, the lowest in the roots. Lastly, the genomic sequences of LkLAC8 in 40 individuals from six naturally distributed populations of Japanese larch were amplified, and a total of 201 SNPs (103 and 98 mutation types of transition and transversion, respectively) were detected; the frequency of the SNPs was 1/19 bp. Nucleotide diversity among the six populations ranged from 0.0034 to 0.0053, which suggested that there were no significant differences among the populations. The LD analysis showed that the LD level decayed rapidly within the increasing length of the LkLAC8 gene. These results implied that LD mapping and association analysis based on candidate gene may be feasible for the marker-assisted breeding of new germplasms with low lignin in Japanese larch.展开更多
Single nucleotide polymorphisms （SNP） of ATP-binding cassette transporter A1 （ABCA1） gene are related to plasma lipid and susceptibility to coronary artery disease （CAD）. Our first goal was to screen all 50 codi...Single nucleotide polymorphisms （SNP） of ATP-binding cassette transporter A1 （ABCA1） gene are related to plasma lipid and susceptibility to coronary artery disease （CAD）. Our first goal was to screen all 50 coding regions of ABCA1 to find new SNPs. Our second goal was to investigate the frequency distribution of R1587K and M883I polymorphisms of ABCA1 gene, which are the variant occurred most frequently, in Chinese people and to evaluate their association with the CAD phenotype and plasma lipids. Methods： Single-strand conformation polymorphism （SSCP） and DNA sequence were used for confirming new SNP of ABCA1, and restriction fragment length polymorphism （RFLP） were applied for confirming genotypes of R1587K and M883I in 112 CAD cases and 108 healthy people. Results： We discovered a new ABCA1 SNP in Chinese population, which converse 233 amino acids from Methionine to Valine （M233V）. This new ABCA1 SNP located in exon7, and might potentially modulate the biological function of lipid metabolism. For R1587K and M883I SNPs, the K allele and I allele frequency was 28.9% and 31.1%, respectively. The K allele at R1587K conferred lower mean values of HDL-C in a dose-dependent manner in both CAD patients and healthy people. However, 883I allele was not associated with plasma lipid level. Neither 1587KK nor 883II associated with increased risk of CAD. Conclusion： Our study finds a potential functional ABCA1 SNPs and revealed K allele of R1587K associated decreased HDL-C level in Chinese population.展开更多
Background:Platinum chemotherapy(CT)remains the backbone of systemic therapy for patients with smallcell lung cancer(SCLC).The nucleotide excision repair(NER)pathway plays a central role in the repair of the DNA damag...Background:Platinum chemotherapy(CT)remains the backbone of systemic therapy for patients with smallcell lung cancer(SCLC).The nucleotide excision repair(NER)pathway plays a central role in the repair of the DNA damage exerted by platinum agents.Alteration in this repair mechanism may affect patients’survival.Materials and Methods:We conducted a retrospective analysis of data from 38 patients with extensive disease(ED)-SCLC who underwent platinum-CT at the Clinical Oncology Unit,Careggi University Hospital,Florence(Italy),from 2015 to 2020.mRNA expression analysis and single nucleotide polymorphism(SNP)characterization of three NER pathway genes—namely ERCC1,ERCC2,and ERCC5—were performed on patient tumor samples.Results:Overall,elevated expression of ERCC genes was observed in SCLC patients compared to healthy controls.Patients with low ERCC1 and ERCC5 expression levels exhibited a better median progression-free survival(mPFS=7.1 vs.4.9 months,p=0.39 for ERCC1 and mPFS=6.9 vs.4.8 months,p=0.093 for ERCC5)and overall survival(mOS=8.7 vs.6.0 months,p=0.4 for ERCC1 and mOS=7.2 vs.6.2 months,p=0.13 for ERCC5).Genotyping analysis of five SNPs of ERCC genes showed a longer survival in patients harboring the wild-type genotype or the heterozygous variant of the ERCC1 rs11615 SNP(p=0.24 for PFS and p=0.14 for OS)and of the rs13181 and rs1799793 ERCC2 SNPs(p=0.43 and p=0.26 for PFS and p=0.21 and p=0.16 for OS,respectively)compared to patients with homozygous mutant genotypes.Conclusions:The comprehensive analysis of ERCC gene expression and SNP variants appears to identify patients who derive greater survival benefits from platinum-CT.展开更多
As a living information and communications system, the genome encodes patterns in single nucleotide polymorphisms (SNPs) reflecting human adaptation that optimizes population survival in differing environments. This p...As a living information and communications system, the genome encodes patterns in single nucleotide polymorphisms (SNPs) reflecting human adaptation that optimizes population survival in differing environments. This paper mathematically models environmentally induced adaptive forces that quantify changes in the distribution of SNP frequencies between populations. We make direct connections between biophysical methods (e.g. minimizing genomic free energy) and concepts in population genetics. Our unbiased computer program scanned a large set of SNPs in the major histocompatibility complex region and flagged an altitude dependency on a SNP associated with response to oxygen deprivation. The statistical power of our double-blind approach is demonstrated in the flagging of mathematical functional correlations of SNP information-based potentials in multiple populations with specific environmental parameters. Furthermore, our approach provides insights for new discoveries on the biology of common variants. This paper demonstrates the power of biophysical modeling of population diversity for better understanding genome-environment interactions in biological phenomenon.展开更多
In sub-Saharan Africa, breast cancer (BC) constitutes a serious public health problem and the genetic basis of its development is remaining poorly understood. Although the SNPs at codon 72 of <em>TP</em>53...In sub-Saharan Africa, breast cancer (BC) constitutes a serious public health problem and the genetic basis of its development is remaining poorly understood. Although the SNPs at codon 72 of <em>TP</em>53 (rs1042522) and at the UTR of <em>SET</em>8 (rs16917496) have both been associated with BC development among Asian and European women, no published data has been reported within African population. We herein report on the impact of these polymorphisms on the risk of BC among Cameroonian women. Blood samples were collected from 111 breast cancer patients and 224 controls. DNA was extracted from each sample and PCR-RFLP was used to investigate the polymorphisms at SNPs rs1042522 of <em>TP</em>53 and rs16917496 of <em>SET</em>8. Association studies were performed according to ethno-linguistic groups and menopausal status. The minor allele “T” of <em>SET</em>8 gene revealed a protective effect in premenopausal women (OR, 0.327;95% CI 0.125 - 0.852) while the CT genotype of <em>SET</em>8 was associated with increased risk of BC (OR, 2.93;95% CI, 1.1 - 7.8). The minor “G” allele of <em>TP</em>53 gene was significantly associated (OR, 2.533;95% CI, 1.455 - 4.408) with increased disease risk in premenopausal women while the CG genotype was significantly associated (OR, 0.39;95% CI, 0.23 - 0.69) with decreased risk of BC. A synergistic genetic interaction at both loci for CC genotype of SET8 and CG genotype of <em>TP</em>53 was associated (OR, 0.46;95% CI, 0.24 - 0.91) with reduced disease risk. No significant association between polymorphisms at the SET8 and <em>TP</em>53 loci and clinical pathologic features of BC was observed. This study suggests significant associations between the SNPs located at the 3’-UTR of <em>SET</em>8 and codon 72 of the <em>TP</em>53 with the risk of breast cancer development among premenopausal women. There is an interaction between <em>TP</em>53 and <em>SET</em>8 genes.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
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
文摘With completion of the Populus genome sequencing project and the availability of many expressed sequence tags （ESTs） databases in forest trees, attention is now rapidly shifting towards the study of individual genetic variation in natural populations. The most abundant form of genetic variation in many eukaryotic species is represented by single nucleotide polymorphisms （SNPs）, which can account for heritable inter-individual differences in complex phenotypes. Unlike humans, the linkage disequilibrium （LD） rapidly decays within candidate genes in forest trees. Thus, SNPs-based candidate gene association studies are considered to be a most effective approach to dissect the complex quantitative traits in forest trees. The present study demonstrates that LD mapping can be used to identify alleles associated with quantitative traits and suggests that this new approach could be particularly useful for performing breeding programs in forest trees. In this review, we will describe the fundamentals, patterns of SNPs distribution and frequency, summarize recent advances in SNPs discovery and LD and comment on the application of LD in the dissection of complex quantitative traits in forest tress. We also put forward the outlook for future SNPs-based association analysis of quantitative traits in forest trees.
文摘Background: More and more chronic kidney disease (CKD) patients are accompanied with hyperuricaemia. As is known, hyperuricaemia is an independent hazard of both cardiovascular diseases (CVD) and chronic kidney diseases. We aim at identifying Single Nucleotide Polymorphism (SNP) difference of hURAT1 (rs7932775) and ABCG2 (rs3825016) on CKD patient with hyperuricemia and/or gout. Methods: All forty-two CKD patients were divided into two groups: hyperuricemia, and control group. 24 hours urine sample and serum were prepared for testing biochemistry parameters. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method is used to analyze hURAT1 and ABCG2 single nucleotide polymorphisms in different groups. Results: 17 patients have CT SNP of hURAT1 (rs7932775) and 13 patients have CT SNP of ABCG2 (rs3825016) in hyperuricemia group, while only 5 persons and 6 persons have the same mutations in control group respectively. 7 patients have CT SNP of both hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group, while only 2 persons have the same mutations in control group. CT mutation rates of hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group were 60.7% (17/28) and 50% (13/28) respectively, higher than that of control group (35.7% (5/14) and 42.8% (6/14)). What is more, Double SNP mutations in both hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group were 25% (7/28), higher than that of control group (14.2%, 2/14). Conclusion: There are higher mutation rates of CT SNP in hURAT1 (rs7932775) and/or ABCG2 (rs3825016) in hyperuricemia group. We can conclude that hyperuricemia is a high risk factor in progress of CKD, which is necessary to take measures of decreasing serum uric acid to delay CKD progress.
基金financially supported by the Fundamental Research Funds for the Central Non-profit Research Institution of CAF(RIF2014-06)the Forestry Industry Research special funds for Public Welfare Projects(201504104)
文摘Nucleotide diversity (pi) and linkage disequilibrium (LD) analysis based on SNP marker could provide a sound basis for choosing an association analysis method. Japanese larch (Larix kaempferi) is an important timber coniferous tree species for pulping and papermaking, but its high lignin content has significantly restricted it application potential. In this study, the LACCASE gene, that plays an important regulatory role for lignin biosynthesis, was selected as research target. The full-length cDNA and genomic sequences of the encoding LkLAC8 gene were isolated from the LACCASE expressed sequence tags of the Japanese larch transcriptome database using the rapid amplification of cDNA ends-polymerase chain reaction (RACE-PCR). The cDNA was determined to be 1940 bp, with an open reading frame (ORF, 1734 bp) that encoded a protein of 577 AA. This protein contains four highly specific Cu2+ binding sites and 11 glycosylation sites, thus belonging to the LACCASE family. The deduced protein sequence shared an 89% identity with the PtaLAC from Pinus taeda. A real-time PCR analysis showed that the LkLAC8 transcript was expressed predominantly in mature xylem, with moderate levels in the immature xylem, cambium and mature leaves, the lowest in the roots. Lastly, the genomic sequences of LkLAC8 in 40 individuals from six naturally distributed populations of Japanese larch were amplified, and a total of 201 SNPs (103 and 98 mutation types of transition and transversion, respectively) were detected; the frequency of the SNPs was 1/19 bp. Nucleotide diversity among the six populations ranged from 0.0034 to 0.0053, which suggested that there were no significant differences among the populations. The LD analysis showed that the LD level decayed rapidly within the increasing length of the LkLAC8 gene. These results implied that LD mapping and association analysis based on candidate gene may be feasible for the marker-assisted breeding of new germplasms with low lignin in Japanese larch.
基金Supported by the Natural Scientific Foundation of China (30471929)
文摘Single nucleotide polymorphisms （SNP） of ATP-binding cassette transporter A1 （ABCA1） gene are related to plasma lipid and susceptibility to coronary artery disease （CAD）. Our first goal was to screen all 50 coding regions of ABCA1 to find new SNPs. Our second goal was to investigate the frequency distribution of R1587K and M883I polymorphisms of ABCA1 gene, which are the variant occurred most frequently, in Chinese people and to evaluate their association with the CAD phenotype and plasma lipids. Methods： Single-strand conformation polymorphism （SSCP） and DNA sequence were used for confirming new SNP of ABCA1, and restriction fragment length polymorphism （RFLP） were applied for confirming genotypes of R1587K and M883I in 112 CAD cases and 108 healthy people. Results： We discovered a new ABCA1 SNP in Chinese population, which converse 233 amino acids from Methionine to Valine （M233V）. This new ABCA1 SNP located in exon7, and might potentially modulate the biological function of lipid metabolism. For R1587K and M883I SNPs, the K allele and I allele frequency was 28.9% and 31.1%, respectively. The K allele at R1587K conferred lower mean values of HDL-C in a dose-dependent manner in both CAD patients and healthy people. However, 883I allele was not associated with plasma lipid level. Neither 1587KK nor 883II associated with increased risk of CAD. Conclusion： Our study finds a potential functional ABCA1 SNPs and revealed K allele of R1587K associated decreased HDL-C level in Chinese population.
文摘Background:Platinum chemotherapy(CT)remains the backbone of systemic therapy for patients with smallcell lung cancer(SCLC).The nucleotide excision repair(NER)pathway plays a central role in the repair of the DNA damage exerted by platinum agents.Alteration in this repair mechanism may affect patients’survival.Materials and Methods:We conducted a retrospective analysis of data from 38 patients with extensive disease(ED)-SCLC who underwent platinum-CT at the Clinical Oncology Unit,Careggi University Hospital,Florence(Italy),from 2015 to 2020.mRNA expression analysis and single nucleotide polymorphism(SNP)characterization of three NER pathway genes—namely ERCC1,ERCC2,and ERCC5—were performed on patient tumor samples.Results:Overall,elevated expression of ERCC genes was observed in SCLC patients compared to healthy controls.Patients with low ERCC1 and ERCC5 expression levels exhibited a better median progression-free survival(mPFS=7.1 vs.4.9 months,p=0.39 for ERCC1 and mPFS=6.9 vs.4.8 months,p=0.093 for ERCC5)and overall survival(mOS=8.7 vs.6.0 months,p=0.4 for ERCC1 and mOS=7.2 vs.6.2 months,p=0.13 for ERCC5).Genotyping analysis of five SNPs of ERCC genes showed a longer survival in patients harboring the wild-type genotype or the heterozygous variant of the ERCC1 rs11615 SNP(p=0.24 for PFS and p=0.14 for OS)and of the rs13181 and rs1799793 ERCC2 SNPs(p=0.43 and p=0.26 for PFS and p=0.21 and p=0.16 for OS,respectively)compared to patients with homozygous mutant genotypes.Conclusions:The comprehensive analysis of ERCC gene expression and SNP variants appears to identify patients who derive greater survival benefits from platinum-CT.
文摘As a living information and communications system, the genome encodes patterns in single nucleotide polymorphisms (SNPs) reflecting human adaptation that optimizes population survival in differing environments. This paper mathematically models environmentally induced adaptive forces that quantify changes in the distribution of SNP frequencies between populations. We make direct connections between biophysical methods (e.g. minimizing genomic free energy) and concepts in population genetics. Our unbiased computer program scanned a large set of SNPs in the major histocompatibility complex region and flagged an altitude dependency on a SNP associated with response to oxygen deprivation. The statistical power of our double-blind approach is demonstrated in the flagging of mathematical functional correlations of SNP information-based potentials in multiple populations with specific environmental parameters. Furthermore, our approach provides insights for new discoveries on the biology of common variants. This paper demonstrates the power of biophysical modeling of population diversity for better understanding genome-environment interactions in biological phenomenon.
文摘In sub-Saharan Africa, breast cancer (BC) constitutes a serious public health problem and the genetic basis of its development is remaining poorly understood. Although the SNPs at codon 72 of <em>TP</em>53 (rs1042522) and at the UTR of <em>SET</em>8 (rs16917496) have both been associated with BC development among Asian and European women, no published data has been reported within African population. We herein report on the impact of these polymorphisms on the risk of BC among Cameroonian women. Blood samples were collected from 111 breast cancer patients and 224 controls. DNA was extracted from each sample and PCR-RFLP was used to investigate the polymorphisms at SNPs rs1042522 of <em>TP</em>53 and rs16917496 of <em>SET</em>8. Association studies were performed according to ethno-linguistic groups and menopausal status. The minor allele “T” of <em>SET</em>8 gene revealed a protective effect in premenopausal women (OR, 0.327;95% CI 0.125 - 0.852) while the CT genotype of <em>SET</em>8 was associated with increased risk of BC (OR, 2.93;95% CI, 1.1 - 7.8). The minor “G” allele of <em>TP</em>53 gene was significantly associated (OR, 2.533;95% CI, 1.455 - 4.408) with increased disease risk in premenopausal women while the CG genotype was significantly associated (OR, 0.39;95% CI, 0.23 - 0.69) with decreased risk of BC. A synergistic genetic interaction at both loci for CC genotype of SET8 and CG genotype of <em>TP</em>53 was associated (OR, 0.46;95% CI, 0.24 - 0.91) with reduced disease risk. No significant association between polymorphisms at the SET8 and <em>TP</em>53 loci and clinical pathologic features of BC was observed. This study suggests significant associations between the SNPs located at the 3’-UTR of <em>SET</em>8 and codon 72 of the <em>TP</em>53 with the risk of breast cancer development among premenopausal women. There is an interaction between <em>TP</em>53 and <em>SET</em>8 genes.
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.
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.
