• PMID: 26380869
• Gene Name: MTHFR
• Condition: Male infertility
• Association: In silico-analysis showed MTHFR-Ala222Val affects enzyme structure and could also change the mRNA properties. The meta-analysis suggested significant association of MTHFR-Ala222Val with risk of male infertility, especially in Asian populations.
• Mutation: MTHFR-Ala222Val
• Population size: 497
• Population details: 497 (242 had unexplained infertility, 255 were healthy controls)
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Male infertility

MTHFR-Ala222Val and male infertility: a study in Iranian men, an updated meta-analysis and an in silico-analysis

Nikzad H, Karimian M, Sareban K, Khoshsokhan M, Hosseinzadeh Colagar A.

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. CI - Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved. FAU - Nikzad, Hossein AU - Nikzad H AD - Gametogenesis Research Center, Kashan University of Medical Sciences, Kashan, Iran; Anatomical Sciences Research Center, Kashan University of Medical Sciences, Kashan, Iran. FAU - Karimian, Mohammad AU - Karimian M AD - 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. FAU - Sareban, Kobra AU - Sareban K AD - Animal Physiology Division, Department of Biology, School of Sciences, Islamic Azad University of Qom, Qom, Iran. FAU - Khoshsokhan, Maryam AU - Khoshsokhan M AD - Animal Physiology Division, Department of Biology, School of Sciences, Islamic Azad University of Qom, Qom, Iran.