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
There have been several epidemiological studies evaluating the potential association between the methylenetetrahydrofolate reductase（MTHFR） A1298 C polymorphism and the risk of male infertility.However,the results o...There have been several epidemiological studies evaluating the potential association between the methylenetetrahydrofolate reductase（MTHFR） A1298 C polymorphism and the risk of male infertility.However,the results obtained were inconsistent.Therefore,we performed a meta-analysis to further examine the association between the MTHFR A1298 C polymorphism and male infertility.A comprehensive search was conducted to identify all eligible studies from the online literature databases published prior to January 15 th,2016.A total of 20 studies with 4293 cases and 4507 controls were included.An odds ratio（OR） and a 95% confidence interval（95% CI） were calculated to assess the strength of the association.A cumulative meta-analysis,sensitivity analysis and assessment of the publication bias were also performed in this study.The results showed that in the overall analysis,the association between the MTHFR A1298 C polymorphism and male infertility was not significant.A stratified analysis by ethnicity revealed a significant increase in the risk of male infertility in the Asian population with the MTHFR A1298 C polymorphism（especially in the heterozygote model：OR=1.20,95% CI=1.01–1.44,P=0.994;the dominant model：OR=1.23,95% CI=1.04–1.45,P=0.996;and the allele model：OR=1.20,95% CI=1.04–1.39,P=0.985） but not in the Caucasian population.In the stratified analyses,no significant association was observed between the different types of male infertility.This meta-analysis suggests the MTHFR A1298 C polymorphism may be a potential risk factor for male infertility,especially in the Asian population.展开更多
To investigate the association of single nucleotide polymorphism 260 and 386 （SNP260 and SNP386） gene with male infertility, an electronic search was performed to identify case-control studies evaluating the relatio...To investigate the association of single nucleotide polymorphism 260 and 386 （SNP260 and SNP386） gene with male infertility, an electronic search was performed to identify case-control studies evaluating the relationship of SNP260 or SNP386 of deleted in azoospermia-like （DAZL） and male infertility. Review Manager 5 was used to process the meta-analysis and other statistical analysis. A total of 139 records were retrieved, of which 13 case-control studies with total 2715 patients and 1835 normozoospermic men were included. SNP260 was found not to play a functional role in male oligo/azoospermia either for Caucasians or for Asians. But for SNP386, models of allele （A/G）, dominant （AA/AG ＋ GG）, co-dominant （AA/AG） and super-dominant （AA ＋ GG/AG） had a strong correlation to spermatogenic failure with related odds ratio being 0.15 （95% confidence interval [95% CI] 0.07 to 0.34, P〈 0.00001）, 0.16 （95% CI 0.07 to 0.35, P〈 0.00001）, 0.15 （95% CI 0.06 to 0.33, P〈 0.00001） and 0.15 （95% CI 0.06 to 0.33, P 〈 0.00001）, respectively. Moreover, this correlation was only found in the Chinese Han population （decreasing around 85% risk of oligo/azoospermia infertility） and not found in India, Japan, and Caucasian countries. Our analysis demonstrated that SNP260 of DAZL did not contribute to oligo/azoospermia while SNP386 was correlated to male infertility. However, this correlation was only found in China with a country-specific and ethnicity-specific manner.展开更多
Background:Recent studies identifying methylenetetrahydrofolate reductase(MTHFR)polymorphisms associated with breast cancer(BC),ovarian cancer(OC),cervical cancer,and endometrial cancer(EC)have reported conflicting re...Background:Recent studies identifying methylenetetrahydrofolate reductase(MTHFR)polymorphisms associated with breast cancer(BC),ovarian cancer(OC),cervical cancer,and endometrial cancer(EC)have reported conflicting results and been underpowered.To clarify the correlation betweenMTHFR mutations and these common female malignancies,we conducted a comprehensive meta-analysis incorporating all eligible publications.Methods:Relevant reports published before January 20,2020,were retrieved from PubMed,Embase,the Cochrane Library,and the China National Knowledge Infrastructure databases.The odds ratio and 95% confidence interval summaries for theMTHFR 677C/T and 1298A/C polymorphisms in BC,OC,cervical cancer,and EC were estimated.Results:A total of 171 studies comprising 56,675 cancer cases and 67,559 controls were included.The results showed a markedly elevated risk of cancer susceptibility related toMTHFR 677C/T based on all genetic models.Similarly,we identified a significant correlation between 1298A/C mutation and cancer risk based on overall comparisons among all models,except the heterozygous model.Moreover,subgroup analysis by cancer type revealed a significantly increased risk of BC associated with 677C/T in the five models and of cervical cancer associated with 1298A/C in some models.Based on ethnicity,significant associations were observed between Asian,African,and mixed populations for 677C/T and the Asian population for 1298A/C.With regard to the sample type used for analysis,we detected a positive association between using blood as the DNA source and cancer risk for 677C/T in all genetic models and for 1298A/C in some genetic models.Further stratification of the results revealed that a notably increased risk was associated with the use of polymerase chain reaction-restriction fragment-length polymorphism or TaqMan as the genotyping method,as well as with the use of population-or hospital-based groups as the controls for 677C/T and 1298A/C,respectively.Conclusion:This meta-analysis suggests thatMTHFR 677C/T and 1298A/C polymorphisms correlate with the risk of common gynecological cancers,with these findings potentially applicable for overall comparisons of related data.展开更多
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.
基金supported by the National Natural Science Foundation of China(No.81302390)Natural Science Foundation of Tianjin Medical University(No.2013KYQ17)
文摘There have been several epidemiological studies evaluating the potential association between the methylenetetrahydrofolate reductase（MTHFR） A1298 C polymorphism and the risk of male infertility.However,the results obtained were inconsistent.Therefore,we performed a meta-analysis to further examine the association between the MTHFR A1298 C polymorphism and male infertility.A comprehensive search was conducted to identify all eligible studies from the online literature databases published prior to January 15 th,2016.A total of 20 studies with 4293 cases and 4507 controls were included.An odds ratio（OR） and a 95% confidence interval（95% CI） were calculated to assess the strength of the association.A cumulative meta-analysis,sensitivity analysis and assessment of the publication bias were also performed in this study.The results showed that in the overall analysis,the association between the MTHFR A1298 C polymorphism and male infertility was not significant.A stratified analysis by ethnicity revealed a significant increase in the risk of male infertility in the Asian population with the MTHFR A1298 C polymorphism（especially in the heterozygote model：OR=1.20,95% CI=1.01–1.44,P=0.994;the dominant model：OR=1.23,95% CI=1.04–1.45,P=0.996;and the allele model：OR=1.20,95% CI=1.04–1.39,P=0.985） but not in the Caucasian population.In the stratified analyses,no significant association was observed between the different types of male infertility.This meta-analysis suggests the MTHFR A1298 C polymorphism may be a potential risk factor for male infertility,especially in the Asian population.
基金ACKNOWLEDGMENTS XHZ is supported by the National Natural Science Foundation of China （No. 81270843 and No. 81160086）.Supplementary information is linked to the online version of the paper on the Asian Journal of Andrology website.
文摘To investigate the association of single nucleotide polymorphism 260 and 386 （SNP260 and SNP386） gene with male infertility, an electronic search was performed to identify case-control studies evaluating the relationship of SNP260 or SNP386 of deleted in azoospermia-like （DAZL） and male infertility. Review Manager 5 was used to process the meta-analysis and other statistical analysis. A total of 139 records were retrieved, of which 13 case-control studies with total 2715 patients and 1835 normozoospermic men were included. SNP260 was found not to play a functional role in male oligo/azoospermia either for Caucasians or for Asians. But for SNP386, models of allele （A/G）, dominant （AA/AG ＋ GG）, co-dominant （AA/AG） and super-dominant （AA ＋ GG/AG） had a strong correlation to spermatogenic failure with related odds ratio being 0.15 （95% confidence interval [95% CI] 0.07 to 0.34, P〈 0.00001）, 0.16 （95% CI 0.07 to 0.35, P〈 0.00001）, 0.15 （95% CI 0.06 to 0.33, P〈 0.00001） and 0.15 （95% CI 0.06 to 0.33, P 〈 0.00001）, respectively. Moreover, this correlation was only found in the Chinese Han population （decreasing around 85% risk of oligo/azoospermia infertility） and not found in India, Japan, and Caucasian countries. Our analysis demonstrated that SNP260 of DAZL did not contribute to oligo/azoospermia while SNP386 was correlated to male infertility. However, this correlation was only found in China with a country-specific and ethnicity-specific manner.
基金This study was supported by grants from the Leading Talent of the"Hundred-Thousand-Ten Thousand Project"in Liaoning(XLYC1905004)Shenyang High-level Innovation Talents Plan(No.RC190403)。
文摘Background:Recent studies identifying methylenetetrahydrofolate reductase(MTHFR)polymorphisms associated with breast cancer(BC),ovarian cancer(OC),cervical cancer,and endometrial cancer(EC)have reported conflicting results and been underpowered.To clarify the correlation betweenMTHFR mutations and these common female malignancies,we conducted a comprehensive meta-analysis incorporating all eligible publications.Methods:Relevant reports published before January 20,2020,were retrieved from PubMed,Embase,the Cochrane Library,and the China National Knowledge Infrastructure databases.The odds ratio and 95% confidence interval summaries for theMTHFR 677C/T and 1298A/C polymorphisms in BC,OC,cervical cancer,and EC were estimated.Results:A total of 171 studies comprising 56,675 cancer cases and 67,559 controls were included.The results showed a markedly elevated risk of cancer susceptibility related toMTHFR 677C/T based on all genetic models.Similarly,we identified a significant correlation between 1298A/C mutation and cancer risk based on overall comparisons among all models,except the heterozygous model.Moreover,subgroup analysis by cancer type revealed a significantly increased risk of BC associated with 677C/T in the five models and of cervical cancer associated with 1298A/C in some models.Based on ethnicity,significant associations were observed between Asian,African,and mixed populations for 677C/T and the Asian population for 1298A/C.With regard to the sample type used for analysis,we detected a positive association between using blood as the DNA source and cancer risk for 677C/T in all genetic models and for 1298A/C in some genetic models.Further stratification of the results revealed that a notably increased risk was associated with the use of polymerase chain reaction-restriction fragment-length polymorphism or TaqMan as the genotyping method,as well as with the use of population-or hospital-based groups as the controls for 677C/T and 1298A/C,respectively.Conclusion:This meta-analysis suggests thatMTHFR 677C/T and 1298A/C polymorphisms correlate with the risk of common gynecological cancers,with these findings potentially applicable for overall comparisons of related data.
