XRCC5 VNTR, XRCC6 -61C>G, and XRCC7 6721G>T Gene Polymorphisms Associated with Male Infertility Risk: Evidences from Case-Control and In Silico Studies.

Danial Jahantigh,Abasalt Hosseinzadeh Colagar

doi:10.1155/2017/4795076

Danial Jahantigh, Abasalt Hosseinzadeh Colagar

Open Access

https://doi.org/10.1155/2017/4795076

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Abstract

We evaluate the association between genetic polymorphisms of XRCC5 VNTR, XRCC6 -61C>G, and XRCC7 6721G>T with male infertility susceptibility. A total of 392 men including 178 infertile males (102 idiopathic azoospermia and 76 severe oligozoospermia) and 214 healthy controls were recruited. XRCC6 -61C>G and XRCC7 6721G>T genotyping was performed by PCR-RFLP whereas XRCC5 VNTR was performed by PCR. The 2R allele and 2R allele carriers of XRCC5 VNTR polymorphism significantly decreased risk of male infertility. The mutant GG genotypes and carriers of the CG and GG genotypes of XRCC6 -61C>G showed increased risk for the male infertility. Furthermore, the G allele of the XRCC6 -61C>G was correlated with increased susceptibility to male infertility. Likewise, the T allele of the XRCC7 6721G>T polymorphism was associated with increased susceptibility to male infertility in azoospermia. In silico analysis predicted that the presence of tandem repeats in XRCC5 gene prompter can be sequence to bind to more nuclear factors. Also, rs2267437 (C>G) variant was located in a well-conserved region in XRCC6 promoter and this variation might lead to differential allelic expression. The XRCC7 6721G>T gene polymorphism occurred in an acceptor-splicing site, but this polymorphism has no severe modification on XRCC7 mRNA splicing. Our results indicate the association of XRCC5 VNTR, XRCC6 -61C>G, and XRCC7 6721G>T gene polymorphisms with male infertility in Iranian men.

Highlights

Male infertility is responsible for 40–50% infertility problems which affects up to one in six couples worldwide [1]
Some evidences declared that DNA damage in human spermatozoa is associated with poor semen quality and low fertilization rates for both in vitro and in vivo fertility, suggesting that sperm DNA damage could be used as a potential predictor of fertility [2, 3]
These studies were approved by the Ethics Committees of University of Mazandaran and informed consent was obtained from each subject before participation

Summary

Introduction

Male infertility is responsible for 40–50% infertility problems which affects up to one in six couples worldwide [1]. Strong evidences support the relationship between genetic polymorphism of genes involved in DNA repair pathways with extra sperm DNA damage and male infertility risk [16,17,18,19,20,21]. Since the Ku protein, Ku70 (XRCC6)/80 (XRCC5), and DNA-PKcs (XRCC7) as critical components of NHEJ play important role in DNA integrity of spermatogenesis and can affect the offspring, we hypothesize that genetic variation of these genes may contribute to male infertility risk. SNPs on the interaction of several factors and motifs, involved in transcription and mRNA splicing

Material and Methods

Results

Discussion

10 XRCC7 6721G