Association between two common transitions of H2BFWT gene and male infertility: a case–control, meta, and structural analysis

Abstract

H2BFWT is one of the testis-specific histones that plays a fundamental role in spermatogenesis, and single nucleotide polymorphisms (SNPs) in this gene may result in male infertility. This study aimed to investigate the association between -9C>T and 368A>G transitions of H2BFWT gene and male infertility through a case-control, meta-analysis, and a bioinformatics approach. In this case-control study, 490 subjects including 240 idiopathic infertile men and 250 healthy controls were included. The -9C>T and 368A>G SNPs genotyping were performed by a PCR-RFLP method. To find eligible studies for meta-analysis, we searched valid scientific databases. The odds ratios with 95% confidence intervals were estimated to find the strength of these associations. Furthermore, the influences of two common transitions on the molecular features of H2BFWT were assessed by in silico tools. Our case-control data revealed that -9C>T is not associated with male infertility. But, there was a significant association between 368A>G and male infertility. In the meta-analysis, five eligible studies were included. Our data revealed significant associations between -9C>T, 368A>G, and male infertility in overall and stratified analyses. Moreover, structural analysis showed that 368A>G could affect the protein structure (SNAP prediction: non-neutral, score: 42, expected accuracy: 71%; SIFT prediction: deleterious, score: -2.55), while -9C>T may affect the binding nucleotide in the promoter region. Based on these findings, two aforementioned polymorphisms were associated with increased risk of male infertility. However, studies with larger sample size and different ethnicities are needed to obtain more accurate conclusions.

Essential Role of Histone Replacement and Modifications in Male Fertility

“…In humans, H2BFWT is a testis-specific histone, is synthesized and aggregated in testes, and single nucleotide polymorphisms (SNPs) in this gene is highly associated with male infertility (Churikov et al, 2004; Lee et al, 2009; Ying et al, 2012; Rafatmanesh et al, 2018; Teimouri et al, 2018). And spermatid-specific H2B (ssH2B) and H2BL1 have been identified and are strongly enriched in round or elongating spermatids, similar to that of TPs and protamines (Moss and Orth, 1993; Unni et al, 1995; Govin et al, 2007).…”

Survivin polymorphisms and susceptibility to prostate cancer: a genetic association study and an in silico analysis

“…Single nucleotide polymorphism could change the gene expression pattern, mRNA structure and protein function (Ebrahimi et al, 2017[ 8 ]; Karimian and Hosseinzadeh Colagar, 2018[ 19 ]; Teimouri et al, 2018[ 37 ]). Numerous evidences suggested that functional genetic polymorphisms could alter the survivin gene expression (Ambrosini et al, 1997[ 3 ]).…”

Methionine Synthase Reductase-A66G and -C524T Single Nucleotide Polymorphisms and Prostate Cancer: A Case-Control Trial

“…The mentioned changes are evaluated by bioinformatics tools. Some previous reports revealed that bioinformatics was an effective device to assess molecular biology and specially to examine the molecular effects of gene polymorphisms (Jamali et al, 2016;Soleimani et al, 2017;Zamni-Badi et al, 2018b;Teimouri et al, 2018;Mobasseri et al, 2019). Therefore, in silico tools were employed in this study to evaluate the effects of C524T polymorphisms on the MTRR molecular aspects.…”