title: MTHFR-Ala222Val and male infertility: a study in Iranian men, an updated meta-analysis and an in silico-analysis.
abstract: Methylenetetrahydrofolate reductase (MTHFR) functions as a main regulatory enzyme in folate metabolism. The association of MTHFR gene Ala222Val polymorphism with male infertility in an Iranian population was investigated by undertaking a meta-analysis and in-silico approach. A genetic association study included 497 men; 242 had unexplained infertility and 255 were healthy controls. Polymerase chain reaction restriction fragment length polymorphism was used for genotyping MTHFR-Ala222Val. OpenMeta[Analyst] software was used to conduct the analysis; 22 studies were identified by searching PubMed and the currently reported genetic association study. A novel in-silico approach was used to analyse the effects of Ala222Val substitution on the structure of mRNA and protein. Genetic association study revealed a significant association of MTHFR-222Val/Val genotype with oligozoospermia (OR 2.32; 95% CI, 1.12 to 4.78; P = 0.0451) and azoospermia (OR 2.59; 95% CI 1.09 to 6.17; P = 0.0314). Meta-analysis for allelic, dominant and codominant models showed a significant association between Ala222Val polymorphism and the risk of male infertility (P < 0.001). In silico-analysis showed MTHFR-Ala222Val affects enzyme structure and could also change the mRNA properties (P = 0.1641; P < 0.2 is significant). The meta-analysis suggested significant association of MTHFR-Ala222Val with risk of male infertility, especially in Asian populations.
authors.affiliation: Gametogenesis Research Center, Kashan University of Medical Sciences, Kashan, Iran; Anatomical Sciences Research Center, Kashan University of Medical Sciences, Kashan, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Nikzad
authors.affiliation: Anatomical Sciences Research Center, Kashan University of Medical Sciences, Kashan, Iran; Department of Molecular and Cell Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar 47416-95447, Iran. Electronic address: mdkarimian@gmail.com.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Karimian
authors.affiliation: Animal Physiology Division, Department of Biology, School of Sciences, Islamic Azad University of Qom, Qom, Iran.
authors.forename: Kobra
authors.initials: K
authors.lastname: Sareban
authors.affiliation: Animal Physiology Division, Department of Biology, School of Sciences, Islamic Azad University of Qom, Qom, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Khoshsokhan
authors.affiliation: Department of Molecular and Cell Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar 47416-95447, Iran. Electronic address: ahcolagar@umz.ac.ir.
authors.forename: Abasalt
authors.initials: A
authors.lastname: Hosseinzadeh Colagar
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D053713:Azoospermia / Q000235:genetics; D016022:Case-Control Studies; D003198:Computer Simulation; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D007492:Iran; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D009845:Oligospermia / Q000235:genetics; D020641:Polymorphism, Single Nucleotide
chemical_list: C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
keywords: Ala222Val polymorphism; Meta-analysis; Methylenetetrahydrofolate reductase gene; idiopathic male infertility; in silico-analysis