Gong Mancheng, Dong Wenjing, He Tingyu, Shi Zhirong, Huang Guiying, Ren Rui, Huang Sichong, Qiu Shaopeng, Yuan Runqiang
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.
Department of Oncology, Zhongshan Affiliated Hospital of Sun Yat-sen University, Zhongshan, Guangdong, 528403, China.
PLoS One. 2015 Mar 20;10(3):e0121147. doi: 10.1371/journal.pone.0121147. eCollection 2015.
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.
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.
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.
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.
亚甲基四氢叶酸还原酶（MTHFR）基因多态性可能是男性不育的一个风险因素。然而，流行病学研究显示，关于MTHFR基因多态性与男性不育风险的研究结果并不一致。因此，我们进行了一项已发表病例对照研究的荟萃分析，以重新审视这一争议。
通过对PubMed、EMBASE、谷歌学术和中国知网（CNKI）进行电子检索，选择符合条件的文献进行本荟萃分析（更新至2014年6月19日）。根据我们的纳入标准和纽卡斯尔-渥太华量表（NOS），仅纳入观察到MTHFR基因多态性与男性不育风险之间关联的高质量研究。采用粗比值比（OR）及95%置信区间（CI）来评估MTHFR基因多态性与男性不育风险之间关联的强度。
共纳入26项研究，涉及5575例病例和5447例对照。总体而言，在固定效应模型（CT + TT vs. CC：OR = 1.34，95% CI：1.23 - 1.46）和随机效应模型（CT + TT vs. CC：OR = 1.39，95% CI：1.19 - 1.62）中，MTHFR 677C>T基因多态性均与男性不育风险存在显著关联。此外，按种族、精子浓度和对照来源进行分层时，在亚洲人、高加索人、无精子症或少精子症亚组以及基于人群和基于医院的对照中均观察到类似结果。然而，仅在少精子症亚组中未观察到显著关联。
我们的结果表明，MTHFR基因多态性与男性不育风险增加有关。需要进一步设计良好的分析研究来证实我们的结论，并评估基因 - 环境与男性不育风险之间的相互作用。
