The c.−190 C>A transversion in promoter region of protamine1 gene as a genetic risk factor for idiopathic oligozoospermia

• Published in: Molecular biology reports 2016-08, Vol.43 (8), p.795-802
• Main Authors: Jamali, Shirin, Karimian, Mohammad, Nikzad, Hossein, Aftabi, Younes
• Format: Article
• Language: English
• Subjects: Adult; Animal Anatomy; Animal Biochemistry; Biomedical and Life Sciences; Case-Control Studies; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Genotype & phenotype; Histology; Humans; Infertility; Life Sciences; Male; Morphology; Oligospermia - genetics; Original Article; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Protamines - genetics; Risk Factors; Sequence Analysis, DNA; Sperm
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-016-4017-8

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.