MTHFR-Ala222Val and male infertility: a study in Iranian men, an updated meta-analysis and an in silico-analysis. Issue 5 (November 2015)

• Record Type: Journal Article
• Authors: Nikzad, Hossein; Karimian, Mohammad; Sareban, Kobra; Khoshsokhan, Maryam; Hosseinzadeh Colagar, Abasalt
• Is Part Of: Reproductive biomedicine online. Volume 31:Issue 5(2015)
• Page Start: 668
• Page End: 680
• Publication Date: 2015-11
• Subjects: Ala222Val polymorphism -- idiopathic male infertility -- in silico-analysis -- Meta-analysis -- Methylenetetrahydrofolate reductase gene; Human reproductive technology -- Periodicals; Human embryo -- Periodicals; Reproduction -- Periodicals; 616.692
• DOI: 10.1016/j.rbmo.2015.07.015
• Languages: English
• ISSNs: 1472-6483

Abstract

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.