title: MTHFR 677C>T polymorphism increases the male infertility risk: a meta-analysis involving 26 studies.
abstract: OBJECTIVE
  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.
authors: 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.
authors: Mancheng
authors: M
authors: Gong
authors: Department of Oncology, Zhongshan Affiliated Hospital of Sun Yat-sen University, Zhongshan, Guangdong, 528403, China.
authors: Wenjing
authors: W
authors: Dong
authors: Department of Reproductive Center, Zhongshan Affiliated Hospital of Sun Yat-sen University, Zhongshan, Guangdong, 528403, China.
authors: Tingyu
authors: T
authors: He
authors: Department of Pharmacy, The Second People's Hospital of Zhuhai, Zhuhai, Guangdong, 519020, China.
authors: Zhirong
authors: Z
authors: Shi
authors: The Second General Department, Zhongshan Affiliated Hospital of Sun Yat-sen University, Zhongshan, Guangdong, 528403, China.
authors: Guiying
authors: G
authors: Huang
authors: Department of Andrology, Zhongshan Affiliated Hospital of Sun Yat-sen University, Zhongshan, Guangdong, 528403, China.
authors: Rui
authors: R
authors: Ren
authors: Department of Andrology, Zhongshan Affiliated Hospital of Sun Yat-sen University, Zhongshan, Guangdong, 528403, China.
authors: Sichong
authors: S
authors: Huang
authors: Department of Urology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.
authors: Shaopeng
authors: S
authors: Qiu
authors: Department of Andrology, Zhongshan Affiliated Hospital of Sun Yat-sen University, Zhongshan, Guangdong, 528403, China.
authors: Runqiang
authors: R
authors: Yuan
mesh_terms: D005006:Ethnicity / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D007248:Infertility, Male / Q000201:enzymology* / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017594:Publication Bias; D012307:Risk Factors; D013094:Spermatozoa / Q000378:metabolism
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)