title: Role of genetic mutations in folate-related enzyme genes on Male Infertility.
abstract: Several studies showed that the genetic mutations in the folate-related enzyme genes might be associated with male infertility; however, the results were still inconsistent. We performed a meta-analysis with trial sequential analysis to investigate the associations between the MTHFR C677T, MTHFR A1298C, MTR A2756G, MTRR A66G mutations and the MTHFR haplotype with the risk of male infertility. Overall, a total of 37 studies were selected. Our meta-analysis showed that the MTHFR C677T mutation was a risk factor for male infertility in both azoospermia and oligoasthenoteratozoospermia patients, especially in Asian population. Men carrying the MTHFR TC haplotype were most liable to suffer infertility while those with CC haplotype had lowest risk. On the other hand, the MTHFR A1298C mutation was not related to male infertility. MTR A2756G and MTRR A66G were potential candidates in the pathogenesis of male infertility, but more case-control studies were required to avoid false-positive outcomes. All of these results were confirmed by the trial sequential analysis. Finally, our meta-analysis with trial sequential analysis proved that the genetic mutations in the folate-related enzyme genes played a significant role in male infertility.
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Ruizhe
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Shen
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Hua
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Zengjun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
mesh_terms: D053627:Asthenozoospermia / Q000235:genetics / Q000473:pathology; D005492:Folic Acid / Q000235:genetics* / Q000378:metabolism; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007248:Infertility, Male / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D009154:Mutation; D009845:Oligospermia / Q000235:genetics / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D005492:Folic Acid; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)