Dataset Information

The association between TNP2 gene polymorphisms and Iranian infertile men with varicocele: A case-control study.

ABSTRACT: Background:Numerous researches have provided great evidence that revealed the relationship between varicocele and sperm DNA damage. Objective:Because of the crucial role of nuclear transition proteins (TPs) in sperm DNA condensation and integrity, this case-control study was designed to study TNP2 gene nucleotide variations in Iranian patients with varicocele. Materials and Methods:PCR-SSCP and DNA sequencing were used to search for mutations in exons 1 & 2 of the TNP2 gene in 156 infertile patients with varicocele and 150 fertile men. Results:The results of sequencing showed three variants at positions c.301C?>?T (p.R101C), c.391C?>?T (p.R131?W), and g.IVS1-26G?>?C (rs8043625) of TNP2 gene. It was found that varicocele risk in men who have the CC genotype of g.IVS1-26G?>?C SNP is higher than those who don't have these genotypes (according to Co-dominant model, Dominant model, Recessive model, and Over-dominant model). The haplotype-based analysis showed that (C/C/T) and (C/T/T) haplotypes were a risk factor of in patients with varicocele compared to controls (OR?=?3.278, p?=?0.000 and OR?=?9.304, p?=?0.038, respectively). Conclusion:Because of the significant difference in the genotype and allele frequencies of g.IVS1-26G?>?C SNP in the intronic region of TNP2 in patients with varicocele compared with controls and also because of the high conservation of this SNP position during evolution, this SNP may be involved in some important processes associated with the expression of this gene like mRNA splicing, but the exact mechanism is not clear.

SUBMITTER: Heidari MM

PROVIDER: S-EPMC6745086 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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The association between <i>TNP2</i> gene polymorphisms and Iranian infertile men with varicocele: A case-control study.

Heidari Mohammad Mehdi MM Danafar Amirhossein A Moezzi Fahime F Khatami Mehri M Talebi Ali Reza AR

International journal of reproductive biomedicine 20190801 8

<h4>Background</h4>Numerous researches have provided great evidence that revealed the relationship between varicocele and sperm DNA damage.<h4>Objective</h4>Because of the crucial role of nuclear transition proteins (TPs) in sperm DNA condensation and integrity, this case-control study was designed to study <i>TNP2</i> gene nucleotide variations in Iranian patients with varicocele.<h4>Materials and methods</h4>PCR-SSCP and DNA sequencing were used to search for mutations in exons 1 & 2 of the <i ...[more]

PMID: 31583373

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Project description:Single nucleotide polymorphisms (SNPs) in a number of genes involved in sperm maturation are considered as one of the main factors for male infertility. The aim of the present case-control study was to examine the association of SNPs in protamine1 (PRM1) and protamine2 (PRM2) genes with idiopathic teratozoospermia. In this case-control study, some SNPs in PRM1 (c.49 C>T, c.102 G>T and c.230A>C) and PRM2 (rs545828790, rs115686767, rs201933708, rs2070923 and rs1646022) were investigated in 30 idiopathic infertile men with teratozoospermia (case group) in comparison with 35 fertile men (controls). Genotyping of SNPs was undertaken using polymerase chain reaction (PCR)-direct sequencing. For PRM1, c.230A>C, as a synonymous polymorphism, was detected in both teratozoospermic men (heterozygous n=26, homozygous minor n=1) allele frequency C(48) A(52) and controls (heterozygous n=15, homozygous minor n=4). All cases and controls were genotyped for rs545828790 in PRM2, a missense polymorphism, as well as rs115686767 and rs201933708, both of which synonymous variants. The findings showed an intronic variant in PRM2 (rs2070923) was also present in both groups. Also, rs1646022, a missense polymorphism, occurred in teratozoospermic men (heterozygous n=10, homozygous minor n=5) and controls (heterozygous n=13, homozygous minor n=2). However, there were no significant differences in SNPs of PRM1 and PRM2 between the two groups, however, for c.230A>C, the frequency of the CA genotype was significantly higher in infertile men with teratozoospermia (P=0.001). We demonstrate that PRM2 G398C and A473C polymorphisms were associated with the teratozoospermia and its genetic variation was in relation to semen quality, sperm apoptosis, and morphology in the Iranian population. This study is a preliminary study and presenting data as part of a future comprehensive study to clinically establish whether these gene polymorphisms are biomarkers for susceptibility to teratozoospermia.

Project description:The etiology of varicocele, a common cause of male factor infertility, remains unclear. Proteomic changes responsible for the underlying pathology of unilateral varicocele have not been evaluated. The objective of this prospective study was to employ proteomic techniques and bioinformatic tools to identify and analyze proteins of interest in infertile men with unilateral varicocele.Spermatozoa from infertile men with unilateral varicocele (n=5) and from fertile men (control; n=5) were pooled in two groups respectively. Proteins were extracted and separated by 1-D SDS-PAGE. Bands were digested and identified on a LTQ-Orbitrap Elite hybrid mass spectrometer system. Bioinformatic analysis identified the pathways and functions of the differentially expressed proteins (DEP).Sperm concentration, motility and morphology were lower, and reactive oxygen species levels were higher in unilateral varicocele patients compared to healthy controls. The total number of proteins identified were 1055, 1010 and 1042 in the fertile group, and 795, 713 and 763 proteins in the unilateral varicocele group. Of the 369 DEP between both groups, 120 proteins were unique to the fertile group and 38 proteins were unique to the unilateral varicocele group. Compared to the control group, 114 proteins were overexpressed while 97 proteins were underexpressed in the unilateral varicocele group. We have identified 29 proteins of interest that are involved in spermatogenesis and other fundamental reproductive events such as sperm maturation, acquisition of sperm motility, hyperactivation, capacitation, acrosome reaction and fertilization. The major functional pathways of the 359 DEP related to the unilateral varicocele group involve metabolism, disease, immune system, gene expression, signal transduction and apoptosis. Functional annotations showed that unilateral varicocele mostly affected small molecule biochemistry and post-translational modification proteins. Proteins expressed uniquely in the unilateral varicocele group were cysteine-rich secretory protein 2 precursor (CRISP2) and arginase-2 (ARG2).The expression of these proteins of interest are altered and possibly functionally compromised in infertile men with unilateral varicocele. If validated, these proteins may lead to potential biomarker(s) and help better understand the mechanism involved in the pathophysiology of unilateral varicocele in infertile men.

Dataset Information

The association between TNP2 gene polymorphisms and Iranian infertile men with varicocele: A case-control study.

Publications

The association between <i>TNP2</i> gene polymorphisms and Iranian infertile men with varicocele: A case-control study.

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