title: The c.-190 C>A transversion in promoter region of protamine1 gene as a genetic risk factor for idiopathic oligozoospermia.
abstract: The genome condensation in the sperm head is resulted with replacing of histones by protamines during spermatogenesis. It is reported that defects in the protamine 1 (PRM1) and/or 2 (PRM2) genes cause male infertility. Located on chromosome 16 (16p13.2) these genes contain numerous unstudied single nucleotide polymorphisms. This study aimed to investigate the association of c.-190 C>A and g.298 G>C transversions that respectively occur in PRM1 and PRM2 genes with idiopathic oligozoospermia. In a case-control study, we collected blood samples from 130 idiopathic oligozoospermia and 130 fertile men. Detection of c.-190 C>A and g.298 G>C polymorphisms performed by direct sequencing and PCR-RFLP methods respectively. An in silico analysis was performed by ASSP, NetGene 2, and PNImodeler online web servers. Our data revealed that g.298 G>C transversion in PRM2 was not associated with oligozoospermia (P > 0.05). Whereas, -190CA and -190AA genotypes in PRM1 gene were associated significantly with increased risk of oligozoospermia (P = 0.0017 and 0.0103, respectively). Also carriers of A allele (CA+AA) for PRM1 c.-190 C>A were at a high risk for oligozoospermia (OR 3.2440, 95 % CI 1.8060-5.8270, P = 0.0001). Further, in silico analysis revealed that c.-190 C>A transversion may alter transcription factor interactions with the promoter region of PRM1. The results revealed that the c.-190 C>A transversion may involve in the susceptibility for oligozoospermia and could be represented as a noninvasive molecular marker for genetic diagnosis of idiopathic oligozoospermia.
authors.affiliation: Genetic Division, Department of Biology, School of Sciences, Islamic Azad University of Ashkezar, Yazd, Iran.
authors.forename: Shirin
authors.initials: S
authors.lastname: Jamali
authors.affiliation: Gametogenesis Research Center, Kashan University of Medical Sciences, Kashan, Iran.|Molecular and Cell Biology Department, Faculty of Basic Sciences, University of Mazandaran, Babolsar, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Karimian
authors.affiliation: Gametogenesis Research Center, Kashan University of Medical Sciences, Kashan, Iran. hnikzad10@gmail.com.|Anatomical Sciences Research Center, Kashan University of Medical Sciences, Kashan, Iran. hnikzad10@gmail.com.
authors.forename: Hossein
authors.initials: H
authors.lastname: Nikzad
authors.affiliation: Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.|Molecular and Cell Biology Department, Faculty of Basic Sciences, University of Mazandaran, Babolsar, Iran.
authors.forename: Younes
authors.initials: Y
authors.lastname: Aftabi
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009845:Oligospermia / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011479:Protamines / Q000235:genetics*; D012307:Risk Factors; D017422:Sequence Analysis, DNA
chemical_list: C082073:PRM1 protein, human; D011479:Protamines
keywords: Idiopathic oligozoospermia; In silico analysis; Male infertility; Protamine genes; Single nucleotide polymorphism