Association of the MTHFR 677C>T and 1298A>C polymorphisms and male infertility risk: a meta-analysis
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(2020) 18:93
REVIEW
Open Access
Association of the MTHFR 677C>T and 1298A>C polymorphisms and male infertility risk: a meta-analysis Fereshteh Aliakbari1, Farkhondeh Pouresmaeili2, Nahal Eshghifar1,3, Zahra Zolghadr4 and Faezeh Azizi5*
Abstract Background and objectives: One of the possible male sterility risk factors are polymorphisms of Methylenetetrahydrofolate reductase (MTHFR). However, the epidemiologic investigations described inconsistent results regarding MTHFR polymorphism and the risk of male infertility. For that reason, we carried out a metaanalysis of published case-control studies to re-examine the controversy. Methods: Electronic searches of Cochrane, EMBASE, Google Scholar, and PubMed were conducted to select eligible studies for this meta-analysis (updated to May 2019). According to our exclusion and inclusion criteria, only highquality studies that remarked the association between MTHFR polymorphisms and male infertility risk were included. The Crude odds ratio (OR) with a confidence interval of 95% (CI) was used to assess the relationship between MTHFR polymorphism and male infertility risk. Results: Thirty-four case-control studies with 9662 cases and 9154 controls concerning 677C/T polymorphism and 22 case-control studies with 5893 cases and 6303 controls concerning 1298A/C polymorphism were recruited. Both MTHFR polymorphisms had significant associations with male infertility risk (CT + TT vs. CC: OR = 1.37, 95% CI: 1.21– 1.55, P = 0.00, I2 = 41.9%); (CC vs. CA + AA: OR = 0.82, 95% CI: 0.52–1.30, P = 0.04, I2 = 50.1%). Further, when stratified by ethnicity, the significant association results were observed in Asians and Caucasians for 677C/T and just Asians for 1298A/C. Conclusions: Some of MTHFR polymorphisms like MTHFR 677C > T are associated with an elevated male infertility risk. To confirm our conclusion and to provide more accurate and complete gene-environment communication with male infertility risk, more analytical studies are needed. Keywords: MTHFR, Polymorphisms, Male infertility
Introduction Infertility is a global problem and according to the World Health Organization, almost one in seven couples are affected by fertility complications [1, 2]. Male infertility is a heterozygous disorder caused by numerous genetic and environmental factors that lead to defects in * Correspondence: [email protected] 5 Genetics Office, Non-Communicable Disease Control Department, Public Health Department, Ministry of Health and Medical Education, Tehran, Iran Full list of author information is available at the end of the article
spermatogenesis [3, 4]. This kind of fertility disorder accounts for 20–50% of causes. According to studies, there is a positive correlation between serum folate concentrations, density, and normal morphology of sperm [5]. Therefore, the Folate pathway is likely to be important in male fertility [6]. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism and plays a vital role in balancing the storage of methyl groups between DNA synthe
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