BACKGROUND Thiopurine-induced leukopenia(TIL)is a life-threatening toxicity and occurs with a high frequency in the Asian population.Although nucleoside diphosphate-linked moiety X-type motif 15(NUDT15)variants signif...BACKGROUND Thiopurine-induced leukopenia(TIL)is a life-threatening toxicity and occurs with a high frequency in the Asian population.Although nucleoside diphosphate-linked moiety X-type motif 15(NUDT15)variants significantly improve the predictive sensitivity of TIL,more than 50%of cases of this toxicity cannot be predicted by this mutation.The potential use of the 6-thioguanine nucleotide(6TGN)level to predict TIL has been explored,but no decisive conclusion has been reached.Can we increase the predictive sensitivity based on 6TGN by subgrouping patients according to their NUDT15 R139C genotypes?AIM To determine the 6TGN cut-off levels after dividing patients into subgroups according to their NUDT15 R139C genotypes.METHODS Patients’clinical and epidemiological characteristics were collected from medical records from July 2014 to February 2017.NUDT15 R139C,thiopurine S methyltransferase,and 6TGN concentrations were measured.RESULTS A total of 411 Crohn’s disease patients were included.TIL was observed in 72 individuals with a median 6TGN level of 323.4 pmol/8×10^8 red blood cells(RBC),which was not different from that of patients without TIL(P=0.071).Then,we compared the 6TGN levels based on NUDT15 R139C.For CC(n=342)and CT(n=65)genotypes,the median 6TGN level in patients with TIL was significantly higher than that in patients without(474.8 vs 306.0 pmol/8×10^8 RBC,P=9.4×10-^5;291.7 vs 217.6 pmol/8×10^8 RBC,P=0.039,respectively).The four TT carriers developed TIL,with a median 6TGN concentration of 135.8 pmol/8×10^8 RBC.The 6TGN cut-off levels were 411.5 and 319.2 pmol/8×108 RBC for the CC and CT groups,respectively.CONCLUSION The predictive sensitivity of TIL based on 6TGN is dramatically increased after subgrouping according to NUDT15 R139C genotypes.Applying 6TGN cut-off levels to adjust thiopurine therapies based on NUDT15 is strongly recommended.展开更多
Aim To synthesize isonucleoside-incorporated oligonucleotides and investigatetheir binding abilities with complementary sequences. Methods The synthesis was performed on DNAsynthesizer, and the binding behavior was in...Aim To synthesize isonucleoside-incorporated oligonucleotides and investigatetheir binding abilities with complementary sequences. Methods The synthesis was performed on DNAsynthesizer, and the binding behavior was investigated by thermal denaturation studies. Results Fourkinds of single isonucleoside containing oligonucleotides were synthesized. The results of thermaldenaturation showed that the existence of isonucleoside decreased the stability of duplex, and theeffect was more obvious when the isonucleoside was in the middle of the sequence. No obviousdifference was observed when 6'-OH of isonucleoside was free or was protected by allyl group.Conclusions The existence of isonucleoside in oli-gonucleotide makes chain twist and decreased thestability of duplex.展开更多
Background and aims:Cessation of nucleoside/nucleotide analogue(Nuc)therapy in patients with HBeAg-negative chronic hepatitis B(CHB)remains controversial.Methods:In this prospective,single-center cohort study,we recru...Background and aims:Cessation of nucleoside/nucleotide analogue(Nuc)therapy in patients with HBeAg-negative chronic hepatitis B(CHB)remains controversial.Methods:In this prospective,single-center cohort study,we recruited 45 patients with HBeAg-negative CHB from The Fifth Medical Center of Chinese People's Liberation Army General Hospital in China's Mainland.Patients were classified into a Nuc cessation group(n?27)and Nuc continuation group(n?18)and followed-up for 36 months.Nuc were stopped after being inactive for at least 4 years(normal alanine aminotransferase(ALT),undetectable hepatitis B virus(HBV)DNA),with liver fibrosisStage1(S1)and inflammationGrade(G1).Results:Within 3 years of follow-up,51.9%patients with Nuc cessation had virological relapse and 14.8%had ALT elevation,while all patients with Nuc continuation had undetectable HBV DNA and normal ALT.The rate of HBsAg loss after Nuc cessation was 22.2%compared with no seroconversion in patients with Nuc continuation.The hepatitis flare rate was 11.1%and there were no cases of hepatic decompensation after Nuc cessation.End of treatment(EOT)HBsAg,HBV RNA,and decline in HBV core-related antigen(HBcrAg)rate were predictive markers for HBsAg seroconversion at 6 months post-Nuc cessation.Conclusion:This study showed favorable HBsAg loss and low hepatitis flare rates after Nuc cessation.EOT HBsAg,HBV RNA,and decline in HBcrAg rate were predictive markers for HBsAg seroconversion at 6 months post-Nuc cessation.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
The physiology of the central and enteric nervous systems and gastric muscle contributes to the complexities encountered in the research and clinical management of gastroparesis. A wide range of prescription drugs tar...The physiology of the central and enteric nervous systems and gastric muscle contributes to the complexities encountered in the research and clinical management of gastroparesis. A wide range of prescription drugs target the underlying neurotransmitter imbalances and adjust nucleotide levels in appropriate tissues, but treatment is unsatisfactory, as our understanding of the condition is far from complete. In this study, computational software is used to focus on the adenine nucleotide, ATP, as a comparative template for the structures of drugs used in gastroparesis treatment. The results demonstrate that muscarinic, dopamine, serotonin (5-HT) and histamine receptor ligand classes relate structurally and differentially to the molecular structure of ATP. In these neurotransmitter classes, compounds do not target cell membrane receptor G-protein signal transduction in a manner that provides a single mechanism for improving gastroparesis symptoms. The exploration of alternative nucleotide-based deficiencies of KATP channels, Na+/K+ATPases and guanine nucleotide directed nitrergic mechanisms should enhance our experimental approach to understanding this condition.展开更多
New water-soluble fluorescent tetracationic imidazolium-based macrocycles are synthesized via a modular SN2 nucleophilic substitution reaction.The positive charge and acidic C-H sites of these macrocycles enable them ...New water-soluble fluorescent tetracationic imidazolium-based macrocycles are synthesized via a modular SN2 nucleophilic substitution reaction.The positive charge and acidic C-H sites of these macrocycles enable them to bind with nucleotides in water,driven by hydrogen bonds and electrostatic interactions.The binding is high affinity for suitable nucleotides.These properties position them as promising candidates for the selective sensing of nucleotides.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
Multiple nucleotide variants(MNVs)are frequently misannotated as separate single-nucleotide variants(SNVs)by widely utilized variant-calling pipelines,presenting substantial challenges in genetic testing and research....Multiple nucleotide variants(MNVs)are frequently misannotated as separate single-nucleotide variants(SNVs)by widely utilized variant-calling pipelines,presenting substantial challenges in genetic testing and research.The role of MNVs in genetic diagnosis remains inadequately characterized,particularly within large disease cohorts.In this study,we comprehensively investigate codon-level MNVs(cMNVs)across 157 hearing loss(HL)-related genes in 11,467 HL cases and 7258 controls from the Chinese Deafness Gene Consortium(CDGC)cohort.A total of 116 cMNVs are identified,occurring in 29.07%of HL cases.Among them,56.03%of cMNVs exhibit functional consequences distinct from constituent SNVs.Moreover,amino acid substitutions exclusive to cMNVs cause more substantial physicochemical disruptions than those associated with SNVs.Notably,51 cMNVs show pathogenicity classifications that diverge from at least one constituent SNV,impacting genetic interpretation in 145 cases.Pathogenicity interpretation of cMNV facilitates definitive genetic diagnoses in eight HL cases that would otherwise have been subject to misdiagnoses or missed diagnoses.These findings provide critical insights into the genomic characteristics,functional impacts,and diagnostic implications of cMNVs,underscoring their clinical significance in genetic diagnosis and emphasizing the necessity for comprehensive and accurate detection and interpretation of cMNVs in genetic testing and research.展开更多
Amoenucles A-F(1-6),six previously undescribed nucleoside derivatives,and two known analogs(7 and 8)were isolated from the culture of Aspergillus amoenus TJ507.Their structures were elucidated through spectroscopic an...Amoenucles A-F(1-6),six previously undescribed nucleoside derivatives,and two known analogs(7 and 8)were isolated from the culture of Aspergillus amoenus TJ507.Their structures were elucidated through spectroscopic analysis,single-crystal X-ray crystallography,and chemical reactions.Notably,3 and 4 represent the first reported instances of nucleosides with an attached pyrrole moiety.Of particular significance,the absolute configuration of the sugar moiety of 1-4 was determined using nuclear magnetic resonance(NMR),electric circular dichroism(ECD)calculations,and a hydrolysis reaction,presenting a potentially valuable method for confirming nucleoside structures.Furthermore,1,2,and 5-8 exhibited potential tumor necrosis factorα(TNF-α)inhibitory activities,which may provide a novel chemical template for the development of agents targeting autoimmune and inflammatory diseases.展开更多
Understanding the genetic diversity–area relationship(GAR)is essential for comprehending how species adapt to environmental changes,as genetic diversity is an indicator of a species’adaptive potential.Variation in e...Understanding the genetic diversity–area relationship(GAR)is essential for comprehending how species adapt to environmental changes,as genetic diversity is an indicator of a species’adaptive potential.Variation in environmental adaptation capacity exists among species and animal taxa with different distribution areas,highlighting the importance of understanding the GAR.To obtain a more comprehensive understanding of the GAR in terrestrial vertebrates,we assessed both haplotype diversity–area and nucleotide diversity–area relationships using 25,453 cytochrome c oxidase subunit I(COI)sequences from 142 amphibian species,574 bird species,and 342 mammal species.We found that both measures of genetic diversity increased with species range size across major animal groups.Nevertheless,the GAR did not differ among animal groups,while haplotype diversity performed better than nucleotide diversity in profiling the GAR,as indicated by higher R2 values.The difference in the modeling fit may stem from the distinct biological and mathematical significance of nucleotide diversity and haplotype diversity.These results suggest that the GAR follows similar rules among different animal taxa.Furthermore,haplotype diversity may serve as a more reliable indicator for assessing the potential effects of area size changes on animal populations and provide better guidance for conserving genetic diversity.展开更多
Genome rearrangement is an important process that leads to genetic diversity,including mutation-related insertions,deletions,or inversions in the genome[1,2].
Aim: To compare the contents of nucleosides from natural Cordyceps sinensis and cultured Cordyceps mycelia, and to study the effect of humidity and heat on the content of nucleosides. Methods: The contents of nucleos...Aim: To compare the contents of nucleosides from natural Cordyceps sinensis and cultured Cordyceps mycelia, and to study the effect of humidity and heat on the content of nucleosides. Methods: The contents of nucleosides were determined by using high performance capillary electrophoresis (HPCE). Beckman P/ACE System 5010 apparatus equipped with a UV detector and a Beckman untreated fused-silica capillary (57 cm 75 mm, 50 cm effective length) was used. Before sample injection, the capillary was rinsed with 1 molL-1 sodium hydroxide solution and running buffer for 5 min, respectively. A voltage of 20 kV was applied for the separation. Pressure injection was 586 kPa for 6 seconds, and the wavelength of detector was 254 nm. The running time was 20 min at 20 oC. The effect of humidity and heat on the contents of nucleosides from natural Cordyceps sinensis and cultured Cordyceps mycelia was observed for 1, 3, 5 and 10 days at temperature 40 oC, and relative humidity 75%. Results: The content of nucleosides from natural Cordyceps sinensis was higher than that from cultured Cordyceps mycelia. But the contents of nucleosides from freshly collected natural Cordyceps sinensis were very low, even below the limit of quantitation. The contents of nucleosides from natural Cordyceps sinensis were significantly increased by humidity and heat, but this phenomenon was not observed in cultured Cordyceps mycelia. Conclusion: There are differences between the nucleosides from natural Cordyceps sinensis and cultured Cordyceps mycelia. The nucleosides in natural Cordyceps sinensis may be derived from the degradation of nucleic acids. This implies that adenosine being used for the quality control of natural Cordyceps sinensis may have to be reconsidered.展开更多
Determination of nucleosides and nucleobases is important for the quality control of Fritillaria unibracteata Hsiao et K.C. Hsia var. wabuensis （FUW） due to their physiological and pharmacological actions. In the pr...Determination of nucleosides and nucleobases is important for the quality control of Fritillaria unibracteata Hsiao et K.C. Hsia var. wabuensis （FUW） due to their physiological and pharmacological actions. In the present study, we developed a sensitive and reliable HPLC-diode-array detection method to simultaneously determine ten nucleosides and nucleobases, including cytosine, uracil, cytidine, uridine, thymine, adenine, inosine, guanosine, thymidine and adenosine. Complete separation of all the analytes was achieved on a Zorbax 300 A 300 Extend C18 column with a gradient of methanol-ultrapure water at a flow rate of 1 mL/min in less than 30 min. The diode-array detector wavelength was set at 260 nm for the UV detection of nucleosides and nucleobases. The optimized method provided good linearity （R2〉0.9993 for all the analytes）, satisfactory precision （RSD〈3.715%）, good repeatability （RSD_〈3.748%） and good recovery （RSD from 97.688% to 102.923%）. In addition, the developed method was successfully applied to simultaneous determination of ten nucleosides and nucleobases from FUW, and their content changes of various cultivation time （1-7 years） were further analyzed for the first time. Our findings were useful for ensuring the cultivation time choice of artificial cultivation, quality control, pharmaceutical studies and clinical efficacy of FUW.展开更多
[Objective]The aim was to research the relationship between nucleotide substitutions rate and selective pressure.[Method]Synonymous and nonsynonymous substitutions and their ratios for some sorghum and maize genes in ...[Objective]The aim was to research the relationship between nucleotide substitutions rate and selective pressure.[Method]Synonymous and nonsynonymous substitutions and their ratios for some sorghum and maize genes in nucleus and organelle genomes were analyzed by statistical method,and comparative analysis of related functional genes were carried out.[Result]The pure selective pressures of the related functional genes were similar between nucleus and chloroplast genomes,but was lower in mitochondrial genome.The significant differences of nucleotide substitution rate between sorghum and maize orthologous genes in nucleus genome,and among different functional genes in nucleus genome were mainly due to the nonsynonymous substitution difference.[Conclusion]The molecular evolutional rate of different functional genes and different lineages were influenced by selective pressure.The differences of molecular evolutional rate among nucleus,chloroplast and mitochondria genomes had no direct relationship with selective pressure.展开更多
[ Objedive] This study was aimed to determine the single nucleotide polymorphisms （SNPs） of IGF-I gene in two breeds, Wanxi white goose and Langde goose. [ Method] Two pair of primers was designed based on chicken a...[ Objedive] This study was aimed to determine the single nucleotide polymorphisms （SNPs） of IGF-I gene in two breeds, Wanxi white goose and Langde goose. [ Method] Two pair of primers was designed based on chicken and porcine genomic sequence to amplify the 5＇ regulatory region of IGF-I, and the sequence was determined and analyzed. [ Result] A total of four SNPs were identified in this region by PCR-SSCP meth- od, that is, A to T at 26 nt, A to G at 215 nt, A to G at 314 nt, and A to T at 325 nt. [ Conclusioa] The two breeds ,wanxi white geese and Langde geese, agree with Hardy-weinberg equilibrium with respect to these SNPS.展开更多
Objective Cyclic nucleotide phosphodiesterase（PDE）is a critical component of the nitric oxide（NO）signaling pathway and plays critical roles in cognition and learning,Parkinson’s disease,attention deficit hyperact...Objective Cyclic nucleotide phosphodiesterase（PDE）is a critical component of the nitric oxide（NO）signaling pathway and plays critical roles in cognition and learning,Parkinson’s disease,attention deficit hyperactivity disorder, psychosis and depression.The PDEs in the brain of guinea pig have not yet been reported.The present study aimed to detect the unknown Pde cDNAs in the brain of guinea pig.Methods Reverse transcription polymerase chain reaction（RT-PCR）and sequence comparison analysis were performed to detect the expression of Pde cDNAs and to assess the identity rates of cDNA and amino acid sequences between guinea pig and human or mouse,respectvely.The RT-PCR primers were located on the conserved region of human PDE and mouse Pde cDNAs.Results Eleven novel Pde cDNAs were detected in the brain of guinea pig（Cavia porcellus）,including CpPde1a,CpPde1b,CpPde2a,CpPde4a,CpPde4d,CpPde5a,CpPde6c,CpPde7b, CpPde8a,CpPde9a,and CpPde10a.The identity rates of the Pde cDNA sequences between guinea pig and human ranged from 83.8%to 94.3%,and those of the amino acid sequences ranged from 91.9%to 100%.The identity rates of Pde cDNA sequences between guinea pig and mouse ranged from 84.6%to 92.1%,and those of amino acid sequences ranged from 91.2% to 99.2%.The average identity rate of the 11 Pde cDNA sequences between guinea pig and human was significantly higher（P 0.01）than that between guinea pig and mouse.The putative partial amino acid sequences of guinea pig contained at least one of the conserved domains of human and mouse PDE proteins.Conclusion These results indicate that the brainexpressed Pde genes are identified in guinea pig,which lays the foundation for further investigating the physiological roles of PDE proteins in the brain.展开更多
Capillary zone electrophoresis has been applied to the analysis of nucleotides. The effects of buffer concentration. pH and other operating conditions on the separation were investigated and optimized. By using the me...Capillary zone electrophoresis has been applied to the analysis of nucleotides. The effects of buffer concentration. pH and other operating conditions on the separation were investigated and optimized. By using the method, separation and identification of nuclotides in swine tissues were completed.展开更多
We quantitatively determined four nucleosides, including cytidine, uridine, guanosine, and adenosine, in Carthamus tinctorius L. and Safflower injection. Separation was performed on a Zorbax Eclipse XDB-18 column usin...We quantitatively determined four nucleosides, including cytidine, uridine, guanosine, and adenosine, in Carthamus tinctorius L. and Safflower injection. Separation was performed on a Zorbax Eclipse XDB-18 column using a gradient elution with mobile phases of 0.05% trifluoroacetic acid （TFA） aqueous solution （A） and methanol （B）. The assay was carried out at a flow rate of 1 mL/min at 25 ℃ with detection at 260 nm. Cytidine, uridine, adenosine and guanosine showed good linearity in the ranges of4.02-503μg/mL （r2= 0.9998）, 9.38-1407 μg/mL （rz = 0.9999）, 80.6-8060μg/mL （r2 = 0.9999） and 2.10---630μg/mL （r2 = 0.9987） with average recoveries of 97.2%, 94.5%, 98.6% and 108.6%, respectively. The contents of cytidine, uridine, adenosine and guanosine in different Carthamus tinctorius L. and Safflower injection were significantly different. This is the first report on the quantitative determination of nucleosides in Carthamus tinctorius L. and Safflower injection.展开更多
Aim To quantitatively determine five nucleosides and nucleobases, including cytidine, uridine, guanosine, adenosine and uracil in different parts of Panax notoginseng. Methods Separation was performed on a Zorbax SB-A...Aim To quantitatively determine five nucleosides and nucleobases, including cytidine, uridine, guanosine, adenosine and uracil in different parts of Panax notoginseng. Methods Separation was performed on a Zorbax SB-Aq column using a gradient elution with mobile phase of 8 mmol^L-1 ammonium acetate aqueous solution （A） and methanol （B）. The assay was carried out at a flow rate of 1 mL·min^-1 at 25 ℃ with the diode-array detection at 260 nm. Results Cytidine, uridine, guanosine, adenosine and uracil had good linearity in the ranges of 1.79 - 57.40 μg·mL^-1 （r^2 = 1.0000）, 3.30 - 105.60 μg·mL^-1 （r^2 = 1.0000）, 3.09 - 98.80 μg·mL^ -1（r^2 = 0.9999）, 2.77 - 88.60 μg·mL^-1 （r^2 = 1.0000） and 0.38 - 12.30 μg·mL ^-1 （r^2 = 1.0000） with average recoveries of 93.9%, 96.5%, 92.7%, 93.2% and 98.8%, respectively. The content of cytidine, uridine, guanosine, adenosine and uracil in different parts of P. notogingeng were significantly different. Conclusion This is the first report on quantitative determination of nucleosides and nucleobases in P notoginseng.展开更多
Aim： To analyze the distribution of the single nucleotide polymorphism （SNP） C677T in the methylenetetrahydrofolate reductase （MTHFR） gene in 355 infertile Chinese patients with idiopathic azoospermia or severe o...Aim： To analyze the distribution of the single nucleotide polymorphism （SNP） C677T in the methylenetetrahydrofolate reductase （MTHFR） gene in 355 infertile Chinese patients with idiopathic azoospermia or severe oligozoospermia and 252 fertile Chinese men as controls to explore the possible association of the SNP and male infertility. Methods： Using the polymerase chain reaction （PCR）-restriction fragment length polymorphism technique, the allele and genotype distribution of SNP C677T in the MTHFR gene were investigated in both patients and controls. Results： The frequencies of allele T （40.9% vs 30.4%, P = 0.002, odds ration [OR] = 1.58, 95% confidence interval [CI]： 1.24-2.02） and mutant homozygote （TT） （18.3% vs. 11.5%, P = 0.023, OR = 1.72, 95% CI： 1.07-2.76） as well as carrier with allele （TT ＋ CT） （63.4% vs. 49.2%, P = 0.0005, OR = 1.79, 95% CI： 1.29-2.48） in infertile patients were significantly higher than those in controls. After patient stratification, the significant differences in distribution of the SNP between each patient subgroup and control group still remained. Conclusion： Our findings indicate that there is an association of SNP C677T in the MTHFR gene with male infertility, suggesting that this polymorphism might be a genetic risk factor for male infertility in Chinese men.展开更多
基金Supported by the National Natural Science Foundation of China,No.81573507,No.81473283,No.81173131,and No.81320108027Guangdong Provincial Key Laboratory Construction Foundation,No.2017B030314030+1 种基金The National Key Research and Development Program,No.2016YFC0905003the 111 Project,No.B16047
文摘BACKGROUND Thiopurine-induced leukopenia(TIL)is a life-threatening toxicity and occurs with a high frequency in the Asian population.Although nucleoside diphosphate-linked moiety X-type motif 15(NUDT15)variants significantly improve the predictive sensitivity of TIL,more than 50%of cases of this toxicity cannot be predicted by this mutation.The potential use of the 6-thioguanine nucleotide(6TGN)level to predict TIL has been explored,but no decisive conclusion has been reached.Can we increase the predictive sensitivity based on 6TGN by subgrouping patients according to their NUDT15 R139C genotypes?AIM To determine the 6TGN cut-off levels after dividing patients into subgroups according to their NUDT15 R139C genotypes.METHODS Patients’clinical and epidemiological characteristics were collected from medical records from July 2014 to February 2017.NUDT15 R139C,thiopurine S methyltransferase,and 6TGN concentrations were measured.RESULTS A total of 411 Crohn’s disease patients were included.TIL was observed in 72 individuals with a median 6TGN level of 323.4 pmol/8×10^8 red blood cells(RBC),which was not different from that of patients without TIL(P=0.071).Then,we compared the 6TGN levels based on NUDT15 R139C.For CC(n=342)and CT(n=65)genotypes,the median 6TGN level in patients with TIL was significantly higher than that in patients without(474.8 vs 306.0 pmol/8×10^8 RBC,P=9.4×10-^5;291.7 vs 217.6 pmol/8×10^8 RBC,P=0.039,respectively).The four TT carriers developed TIL,with a median 6TGN concentration of 135.8 pmol/8×10^8 RBC.The 6TGN cut-off levels were 411.5 and 319.2 pmol/8×108 RBC for the CC and CT groups,respectively.CONCLUSION The predictive sensitivity of TIL based on 6TGN is dramatically increased after subgrouping according to NUDT15 R139C genotypes.Applying 6TGN cut-off levels to adjust thiopurine therapies based on NUDT15 is strongly recommended.
文摘Aim To synthesize isonucleoside-incorporated oligonucleotides and investigatetheir binding abilities with complementary sequences. Methods The synthesis was performed on DNAsynthesizer, and the binding behavior was investigated by thermal denaturation studies. Results Fourkinds of single isonucleoside containing oligonucleotides were synthesized. The results of thermaldenaturation showed that the existence of isonucleoside decreased the stability of duplex, and theeffect was more obvious when the isonucleoside was in the middle of the sequence. No obviousdifference was observed when 6'-OH of isonucleoside was free or was protected by allyl group.Conclusions The existence of isonucleoside in oli-gonucleotide makes chain twist and decreased thestability of duplex.
基金supported by the Beijing Municipal Foundation for Clinical Research[Z181100001718033]the Project for Prevention and Treatment of AIDS and Viral Hepatitis[2018ZX10301-404]the National Major Science and Technology Project of China[2019YFC0840704].
文摘Background and aims:Cessation of nucleoside/nucleotide analogue(Nuc)therapy in patients with HBeAg-negative chronic hepatitis B(CHB)remains controversial.Methods:In this prospective,single-center cohort study,we recruited 45 patients with HBeAg-negative CHB from The Fifth Medical Center of Chinese People's Liberation Army General Hospital in China's Mainland.Patients were classified into a Nuc cessation group(n?27)and Nuc continuation group(n?18)and followed-up for 36 months.Nuc were stopped after being inactive for at least 4 years(normal alanine aminotransferase(ALT),undetectable hepatitis B virus(HBV)DNA),with liver fibrosisStage1(S1)and inflammationGrade(G1).Results:Within 3 years of follow-up,51.9%patients with Nuc cessation had virological relapse and 14.8%had ALT elevation,while all patients with Nuc continuation had undetectable HBV DNA and normal ALT.The rate of HBsAg loss after Nuc cessation was 22.2%compared with no seroconversion in patients with Nuc continuation.The hepatitis flare rate was 11.1%and there were no cases of hepatic decompensation after Nuc cessation.End of treatment(EOT)HBsAg,HBV RNA,and decline in HBV core-related antigen(HBcrAg)rate were predictive markers for HBsAg seroconversion at 6 months post-Nuc cessation.Conclusion:This study showed favorable HBsAg loss and low hepatitis flare rates after Nuc cessation.EOT HBsAg,HBV RNA,and decline in HBcrAg rate were predictive markers for HBsAg seroconversion at 6 months post-Nuc cessation.
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.
文摘The physiology of the central and enteric nervous systems and gastric muscle contributes to the complexities encountered in the research and clinical management of gastroparesis. A wide range of prescription drugs target the underlying neurotransmitter imbalances and adjust nucleotide levels in appropriate tissues, but treatment is unsatisfactory, as our understanding of the condition is far from complete. In this study, computational software is used to focus on the adenine nucleotide, ATP, as a comparative template for the structures of drugs used in gastroparesis treatment. The results demonstrate that muscarinic, dopamine, serotonin (5-HT) and histamine receptor ligand classes relate structurally and differentially to the molecular structure of ATP. In these neurotransmitter classes, compounds do not target cell membrane receptor G-protein signal transduction in a manner that provides a single mechanism for improving gastroparesis symptoms. The exploration of alternative nucleotide-based deficiencies of KATP channels, Na+/K+ATPases and guanine nucleotide directed nitrergic mechanisms should enhance our experimental approach to understanding this condition.
基金Zhejiang Provincial Natural Science Foundation of China(Nos.LR24B020003 and LQ24B020003)Science and Technology Project of Taizhou City(No.24gyb17)for financial support。
文摘New water-soluble fluorescent tetracationic imidazolium-based macrocycles are synthesized via a modular SN2 nucleophilic substitution reaction.The positive charge and acidic C-H sites of these macrocycles enable them to bind with nucleotides in water,driven by hydrogen bonds and electrostatic interactions.The binding is high affinity for suitable nucleotides.These properties position them as promising candidates for the selective sensing of nucleotides.
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 Key Project of the National Natural Science Foundation of China(82030030)the National Natural Science Foundation of China(82171836)+1 种基金the Science and Technology Department of Sichuan Province(2024NSFSC0648)the 1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYJC20002).
文摘Multiple nucleotide variants(MNVs)are frequently misannotated as separate single-nucleotide variants(SNVs)by widely utilized variant-calling pipelines,presenting substantial challenges in genetic testing and research.The role of MNVs in genetic diagnosis remains inadequately characterized,particularly within large disease cohorts.In this study,we comprehensively investigate codon-level MNVs(cMNVs)across 157 hearing loss(HL)-related genes in 11,467 HL cases and 7258 controls from the Chinese Deafness Gene Consortium(CDGC)cohort.A total of 116 cMNVs are identified,occurring in 29.07%of HL cases.Among them,56.03%of cMNVs exhibit functional consequences distinct from constituent SNVs.Moreover,amino acid substitutions exclusive to cMNVs cause more substantial physicochemical disruptions than those associated with SNVs.Notably,51 cMNVs show pathogenicity classifications that diverge from at least one constituent SNV,impacting genetic interpretation in 145 cases.Pathogenicity interpretation of cMNV facilitates definitive genetic diagnoses in eight HL cases that would otherwise have been subject to misdiagnoses or missed diagnoses.These findings provide critical insights into the genomic characteristics,functional impacts,and diagnostic implications of cMNVs,underscoring their clinical significance in genetic diagnosis and emphasizing the necessity for comprehensive and accurate detection and interpretation of cMNVs in genetic testing and research.
基金supported by the National Natural Science Foundation for Distinguished Young Scholars (No. 81725021)the National Natural Science Foundation of China (Nos.82003633 and 82173705)。
文摘Amoenucles A-F(1-6),six previously undescribed nucleoside derivatives,and two known analogs(7 and 8)were isolated from the culture of Aspergillus amoenus TJ507.Their structures were elucidated through spectroscopic analysis,single-crystal X-ray crystallography,and chemical reactions.Notably,3 and 4 represent the first reported instances of nucleosides with an attached pyrrole moiety.Of particular significance,the absolute configuration of the sugar moiety of 1-4 was determined using nuclear magnetic resonance(NMR),electric circular dichroism(ECD)calculations,and a hydrolysis reaction,presenting a potentially valuable method for confirming nucleoside structures.Furthermore,1,2,and 5-8 exhibited potential tumor necrosis factorα(TNF-α)inhibitory activities,which may provide a novel chemical template for the development of agents targeting autoimmune and inflammatory diseases.
基金supported by the National Natural Science Foundation of China(32130013,32070434)the National Key Research and Development Program of China(2022YFC2601601)+1 种基金the Second Tibetan Plateau Scientific Expedition and Research(STEP)program(2019QZKK05010112,2019QZKK0304-02)Hainan Tropical Rainforest Conservation Research Project,ZDYF2023RDYL01(supported by the Hainan Institute of National Park,HINP,KY-24ZK02).
文摘Understanding the genetic diversity–area relationship(GAR)is essential for comprehending how species adapt to environmental changes,as genetic diversity is an indicator of a species’adaptive potential.Variation in environmental adaptation capacity exists among species and animal taxa with different distribution areas,highlighting the importance of understanding the GAR.To obtain a more comprehensive understanding of the GAR in terrestrial vertebrates,we assessed both haplotype diversity–area and nucleotide diversity–area relationships using 25,453 cytochrome c oxidase subunit I(COI)sequences from 142 amphibian species,574 bird species,and 342 mammal species.We found that both measures of genetic diversity increased with species range size across major animal groups.Nevertheless,the GAR did not differ among animal groups,while haplotype diversity performed better than nucleotide diversity in profiling the GAR,as indicated by higher R2 values.The difference in the modeling fit may stem from the distinct biological and mathematical significance of nucleotide diversity and haplotype diversity.These results suggest that the GAR follows similar rules among different animal taxa.Furthermore,haplotype diversity may serve as a more reliable indicator for assessing the potential effects of area size changes on animal populations and provide better guidance for conserving genetic diversity.
基金supported by grants(92168103,32171417,2019CXJQ01)from the National Nature Science Foundation of China,Shanghai Municipal GovernmentPeak Disciplines(Type IV)of Institutions of Higher Learning in Shanghai.
文摘Genome rearrangement is an important process that leads to genetic diversity,including mutation-related insertions,deletions,or inversions in the genome[1,2].
文摘Aim: To compare the contents of nucleosides from natural Cordyceps sinensis and cultured Cordyceps mycelia, and to study the effect of humidity and heat on the content of nucleosides. Methods: The contents of nucleosides were determined by using high performance capillary electrophoresis (HPCE). Beckman P/ACE System 5010 apparatus equipped with a UV detector and a Beckman untreated fused-silica capillary (57 cm 75 mm, 50 cm effective length) was used. Before sample injection, the capillary was rinsed with 1 molL-1 sodium hydroxide solution and running buffer for 5 min, respectively. A voltage of 20 kV was applied for the separation. Pressure injection was 586 kPa for 6 seconds, and the wavelength of detector was 254 nm. The running time was 20 min at 20 oC. The effect of humidity and heat on the contents of nucleosides from natural Cordyceps sinensis and cultured Cordyceps mycelia was observed for 1, 3, 5 and 10 days at temperature 40 oC, and relative humidity 75%. Results: The content of nucleosides from natural Cordyceps sinensis was higher than that from cultured Cordyceps mycelia. But the contents of nucleosides from freshly collected natural Cordyceps sinensis were very low, even below the limit of quantitation. The contents of nucleosides from natural Cordyceps sinensis were significantly increased by humidity and heat, but this phenomenon was not observed in cultured Cordyceps mycelia. Conclusion: There are differences between the nucleosides from natural Cordyceps sinensis and cultured Cordyceps mycelia. The nucleosides in natural Cordyceps sinensis may be derived from the degradation of nucleic acids. This implies that adenosine being used for the quality control of natural Cordyceps sinensis may have to be reconsidered.
基金The Specialized Research Fund for the Doctoral Program of Higher Education of China(Grant No.20115103110009)"211"Project Double-Support Plan of Sichuan Agricultural Un iversity(Grant No.03570313)Modernization of Chinese Traditional Medicines in Hainan Province(Grant No.ZY201410)
文摘Determination of nucleosides and nucleobases is important for the quality control of Fritillaria unibracteata Hsiao et K.C. Hsia var. wabuensis （FUW） due to their physiological and pharmacological actions. In the present study, we developed a sensitive and reliable HPLC-diode-array detection method to simultaneously determine ten nucleosides and nucleobases, including cytosine, uracil, cytidine, uridine, thymine, adenine, inosine, guanosine, thymidine and adenosine. Complete separation of all the analytes was achieved on a Zorbax 300 A 300 Extend C18 column with a gradient of methanol-ultrapure water at a flow rate of 1 mL/min in less than 30 min. The diode-array detector wavelength was set at 260 nm for the UV detection of nucleosides and nucleobases. The optimized method provided good linearity （R2〉0.9993 for all the analytes）, satisfactory precision （RSD〈3.715%）, good repeatability （RSD_〈3.748%） and good recovery （RSD from 97.688% to 102.923%）. In addition, the developed method was successfully applied to simultaneous determination of ten nucleosides and nucleobases from FUW, and their content changes of various cultivation time （1-7 years） were further analyzed for the first time. Our findings were useful for ensuring the cultivation time choice of artificial cultivation, quality control, pharmaceutical studies and clinical efficacy of FUW.
基金Supported by Natural Science Foundation of Jiangsu Province(BK2009235)~~
文摘[Objective]The aim was to research the relationship between nucleotide substitutions rate and selective pressure.[Method]Synonymous and nonsynonymous substitutions and their ratios for some sorghum and maize genes in nucleus and organelle genomes were analyzed by statistical method,and comparative analysis of related functional genes were carried out.[Result]The pure selective pressures of the related functional genes were similar between nucleus and chloroplast genomes,but was lower in mitochondrial genome.The significant differences of nucleotide substitution rate between sorghum and maize orthologous genes in nucleus genome,and among different functional genes in nucleus genome were mainly due to the nonsynonymous substitution difference.[Conclusion]The molecular evolutional rate of different functional genes and different lineages were influenced by selective pressure.The differences of molecular evolutional rate among nucleus,chloroplast and mitochondria genomes had no direct relationship with selective pressure.
文摘[ Objedive] This study was aimed to determine the single nucleotide polymorphisms （SNPs） of IGF-I gene in two breeds, Wanxi white goose and Langde goose. [ Method] Two pair of primers was designed based on chicken and porcine genomic sequence to amplify the 5＇ regulatory region of IGF-I, and the sequence was determined and analyzed. [ Result] A total of four SNPs were identified in this region by PCR-SSCP meth- od, that is, A to T at 26 nt, A to G at 215 nt, A to G at 314 nt, and A to T at 325 nt. [ Conclusioa] The two breeds ,wanxi white geese and Langde geese, agree with Hardy-weinberg equilibrium with respect to these SNPS.
基金supported by the National Natural Science Foundation of China(No.31070928,30600198)the Natural Science Foundation of Guangdong Province,China(No.06301101)the Medical Research Program of Guangdong Province,China(No.A2010259)
文摘Objective Cyclic nucleotide phosphodiesterase（PDE）is a critical component of the nitric oxide（NO）signaling pathway and plays critical roles in cognition and learning,Parkinson’s disease,attention deficit hyperactivity disorder, psychosis and depression.The PDEs in the brain of guinea pig have not yet been reported.The present study aimed to detect the unknown Pde cDNAs in the brain of guinea pig.Methods Reverse transcription polymerase chain reaction（RT-PCR）and sequence comparison analysis were performed to detect the expression of Pde cDNAs and to assess the identity rates of cDNA and amino acid sequences between guinea pig and human or mouse,respectvely.The RT-PCR primers were located on the conserved region of human PDE and mouse Pde cDNAs.Results Eleven novel Pde cDNAs were detected in the brain of guinea pig（Cavia porcellus）,including CpPde1a,CpPde1b,CpPde2a,CpPde4a,CpPde4d,CpPde5a,CpPde6c,CpPde7b, CpPde8a,CpPde9a,and CpPde10a.The identity rates of the Pde cDNA sequences between guinea pig and human ranged from 83.8%to 94.3%,and those of the amino acid sequences ranged from 91.9%to 100%.The identity rates of Pde cDNA sequences between guinea pig and mouse ranged from 84.6%to 92.1%,and those of amino acid sequences ranged from 91.2% to 99.2%.The average identity rate of the 11 Pde cDNA sequences between guinea pig and human was significantly higher（P 0.01）than that between guinea pig and mouse.The putative partial amino acid sequences of guinea pig contained at least one of the conserved domains of human and mouse PDE proteins.Conclusion These results indicate that the brainexpressed Pde genes are identified in guinea pig,which lays the foundation for further investigating the physiological roles of PDE proteins in the brain.
文摘Capillary zone electrophoresis has been applied to the analysis of nucleotides. The effects of buffer concentration. pH and other operating conditions on the separation were investigated and optimized. By using the method, separation and identification of nuclotides in swine tissues were completed.
基金Program for Changjiang Scholar and Innovative Team in University(Grant No.985-2-063-112)
文摘We quantitatively determined four nucleosides, including cytidine, uridine, guanosine, and adenosine, in Carthamus tinctorius L. and Safflower injection. Separation was performed on a Zorbax Eclipse XDB-18 column using a gradient elution with mobile phases of 0.05% trifluoroacetic acid （TFA） aqueous solution （A） and methanol （B）. The assay was carried out at a flow rate of 1 mL/min at 25 ℃ with detection at 260 nm. Cytidine, uridine, adenosine and guanosine showed good linearity in the ranges of4.02-503μg/mL （r2= 0.9998）, 9.38-1407 μg/mL （rz = 0.9999）, 80.6-8060μg/mL （r2 = 0.9999） and 2.10---630μg/mL （r2 = 0.9987） with average recoveries of 97.2%, 94.5%, 98.6% and 108.6%, respectively. The contents of cytidine, uridine, adenosine and guanosine in different Carthamus tinctorius L. and Safflower injection were significantly different. This is the first report on the quantitative determination of nucleosides in Carthamus tinctorius L. and Safflower injection.
文摘Aim To quantitatively determine five nucleosides and nucleobases, including cytidine, uridine, guanosine, adenosine and uracil in different parts of Panax notoginseng. Methods Separation was performed on a Zorbax SB-Aq column using a gradient elution with mobile phase of 8 mmol^L-1 ammonium acetate aqueous solution （A） and methanol （B）. The assay was carried out at a flow rate of 1 mL·min^-1 at 25 ℃ with the diode-array detection at 260 nm. Results Cytidine, uridine, guanosine, adenosine and uracil had good linearity in the ranges of 1.79 - 57.40 μg·mL^-1 （r^2 = 1.0000）, 3.30 - 105.60 μg·mL^-1 （r^2 = 1.0000）, 3.09 - 98.80 μg·mL^ -1（r^2 = 0.9999）, 2.77 - 88.60 μg·mL^-1 （r^2 = 1.0000） and 0.38 - 12.30 μg·mL ^-1 （r^2 = 1.0000） with average recoveries of 93.9%, 96.5%, 92.7%, 93.2% and 98.8%, respectively. The content of cytidine, uridine, guanosine, adenosine and uracil in different parts of P. notogingeng were significantly different. Conclusion This is the first report on quantitative determination of nucleosides and nucleobases in P notoginseng.
基金Acknowledgment This work was supported by the National High Tech- nology Research and Development Program of China （Grants 2004AA216090 and 2002BA711A08）, National Basic Research Program of China （Grant 2004Cb518805）, the Natural National Science Foundation of China （Grant 30470960） and the China Medical Board of New York.
文摘Aim： To analyze the distribution of the single nucleotide polymorphism （SNP） C677T in the methylenetetrahydrofolate reductase （MTHFR） gene in 355 infertile Chinese patients with idiopathic azoospermia or severe oligozoospermia and 252 fertile Chinese men as controls to explore the possible association of the SNP and male infertility. Methods： Using the polymerase chain reaction （PCR）-restriction fragment length polymorphism technique, the allele and genotype distribution of SNP C677T in the MTHFR gene were investigated in both patients and controls. Results： The frequencies of allele T （40.9% vs 30.4%, P = 0.002, odds ration [OR] = 1.58, 95% confidence interval [CI]： 1.24-2.02） and mutant homozygote （TT） （18.3% vs. 11.5%, P = 0.023, OR = 1.72, 95% CI： 1.07-2.76） as well as carrier with allele （TT ＋ CT） （63.4% vs. 49.2%, P = 0.0005, OR = 1.79, 95% CI： 1.29-2.48） in infertile patients were significantly higher than those in controls. After patient stratification, the significant differences in distribution of the SNP between each patient subgroup and control group still remained. Conclusion： Our findings indicate that there is an association of SNP C677T in the MTHFR gene with male infertility, suggesting that this polymorphism might be a genetic risk factor for male infertility in Chinese men.
