• PMID: 25793386
• Gene Name: MTHFR
• Condition: Male infertility
• Association: The results indicated that the MTHFR polymorphism is associated with an increased risk of male infertility.
• Mutation: MTHFR 677C>T polymorphism
• Population size: 11022
• Population details: 11022 (5575 cases, 5447 controls)
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Male infertility

MTHFR 677C>T polymorphism increases the male infertility risk: a meta-analysis involving 26 studies

Gong M, Dong W, He T, Shi Z, Huang G, Ren R, Huang S, Qiu S, Yuan R.

BACKGROUND AND OBJECTIVES: Methylenetetrahydrofolate reductase (MTHFR) polymorphism may be a risk factor for male infertility. However, the epidemiologic studies showed inconsistent results regarding MTHFR polymorphism and the risk of male infertility. Therefore, we performed a meta-analysis of published case-control studies to re-examine the controversy. METHODS: Electronic searches of PubMed, EMBASE, Google Scholar and China National Knowledge Infrastructure (CNKI) were conducted to select eligible literatures for this meta-analysis (updated to June 19, 2014). According to our inclusion criteria and the Newcastle-Ottawa Scale (NOS), only high quality studies that observed the association between MTHFR polymorphism and male infertility risk were included. Crude odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of association between the MTHFR polymorphism and male infertility risk. RESULTS: Twenty-six studies involving 5,575 cases and 5,447 controls were recruited. Overall, MTHFR 677C>T polymorphism showed significant associations with male infertility risk in both fixed effects (CT+TT vs. CC: OR = 1.34, 95% CI: 1.23-1.46) and random effects models (CT+TT vs. CC: OR = 1.39, 95% CI: 1.19-1.62). Further, when stratified by ethnicity, sperm concentration and control sources, the similar results were observed in Asians, Caucasians, Azoo or OAT subgroup and both in population-based and hospital-based controls. Nevertheless, no significant association was only observed in oligo subgroup. CONCLUSIONS: Our results indicated that the MTHFR polymorphism is associated with an increased risk of male infertility. Further well-designed analytical studies are necessary to confirm our conclusions and evaluate gene-environment interactions with male infertility risk. FAU - Gong, Mancheng AU - Gong M AD - Department of Urology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510080, China; Department of Andrology, Zhongshan Affiliated Hospital of Sun Yat-sen University, Zhongshan, Guangdong, 528403, China. FAU - Dong, Wenjing AU - Dong W AD - Department of Oncology, Zhongshan Affiliated Hospital of Sun Yat-sen University, Zhongshan, Guangdong, 528403, China. FAU - He, Tingyu AU - He T AD - Department of Reproductive Center, Zhongshan Affiliated Hospital of Sun Yat-sen University, Zhongshan, Guangdong, 528403, China. FAU - Shi, Zhirong AU - Shi Z AD - Department of Pharmacy, The Second People's Hospital of Zhuhai, Zhuhai, Guangdong, 519020, China. FAU - Huang, Guiying AU - Huang G AD - The Second General Department, Zhongshan Affiliated Hospital of Sun Yat-sen University, Zhongshan, Guangdong, 528403, China. FAU - Ren, Rui AU - Ren R AD - Department of Andrology, Zhongshan Affiliated Hospital of Sun Yat-sen University, Zhongshan, Guangdong, 528403, China. FAU - Huang, Sichong AU - Huang S AD - Department of Andrology, Zhongshan Affiliated Hospital of Sun Yat-sen University, Zhongshan, Guangdong, 528403, China. FAU - Qiu, Shaopeng AU - Qiu S AD - Department of Urology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.