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

Nikzad, H. and Karimian, M. and Sareban, K. and Khoshsokhan, M. and Hosseinzadeh Colagar, A. (2015) MTHFR-Ala222Val and male infertility: A study in Iranian men, an updated meta-analysis and an in silico-analysis. Reproductive BioMedicine Online, 31 (5). pp. 668-680.

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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. OpenMetaAnalyst 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. © 2015 Reproductive Healthcare Ltd.

Item Type: Article
Additional Information: cited By 3
Uncontrolled Keywords: 5,10 methylenetetrahydrofolate reductase (FADH2); methylenetetrahydrofolate reductase (NADPH2); MTHFR protein, human, amino acid sequence; Article; computer model; controlled study; DNA polymorphism; DNA sequence; enzyme structure; folate metabolism; gene; gene frequency; genetic association; genotype; human; human experiment; hydrophobicity; Iranian people; male; male infertility; meta analysis; MTHFR gene; normal human; oligospermia; polymerase chain reaction; protein function; restriction fragment length polymorphism; semen analysis; adult; Asian continental ancestry group; azoospermia; case control study; computer simulation; genetic association study; genetic predisposition; genetics; Iran; male infertility; single nucleotide polymorphism, Adult; Asian Continental Ancestry Group; Azoospermia; Case-Control Studies; Computer Simulation; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Infertility, Male; Iran; Male; Methylenetetrahydrofolate Reductase (NADPH2); Oligospermia; Polymorphism, Single Nucleotide
Subjects: Biochemistry, Genetics and Molecular Biology
Divisions: Faculty of Medicine > Basic Sciences > Department of Anatomy
Depositing User: editor . 2
Date Deposited: 08 Mar 2017 17:08
Last Modified: 08 Mar 2017 17:08
URI: http://eprints.kaums.ac.ir/id/eprint/249

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