The c.‐190 C>A transversion in promoter region of protamine 1 gene as a genetic risk factor in Egyptian men with idiopathic infertility

Protamines are considered the most important structure in the sperm nucleus, and they are proteins with a significantly large amount of amino acids carrying a positive charge, which allows the formation of the tight package of the genomic DNA in the spermatozoa. Many authors studied the abnormalities in the protamine 1 (PRM1) and/or protamine 2 (PRM2) genes and reported their possible association with male infertility. The chromosome 16 (16p13.2) carries these genes containing multiple undiscovered single nucleotide polymorphisms. The aim of the present study was to investigate the association of c.‐190 C>A transversions that occur in PRM1 with idiopathic infertility in a sample of Egyptian men. It was a case–control study, and blood samples were collected from sixty male patients complaining of idiopathic infertility and forty healthy fertile males. The c.‐190 C>A transversion in promotor region protamine 1 gene (rs2301365) was assessed by 5' nuclease assay, using Rotor‐Gene Q real‐time PCR system. The results of the present study revealed that CA and AA genotypes in PRM1 gene were associated significantly with low sperm concentration and decreased sperm motility (p = 0.001). Cases carrying A allele had a 6.05‐fold increased risk for idiopathic infertility than cases carrying the C allele (OR: 6.05, 95% CI: 2.038–17.98 p statistically significant ≤0.05). Analysis of the results revealed that the c.‐190 C>A transversion may be involved in the development of male infertility.

[1]  M. Taşpınar,et al.  Genetic Polymorphisms in PRM1, PRM2, and YBX2 Genes are Associated with Male Factor Infertility. , 2017, Genetic testing and molecular biomarkers.

[2]  H. Nikzad,et al.  The c.−190 C>A transversion in promoter region of protamine1 gene as a genetic risk factor for idiopathic oligozoospermia , 2016, Molecular Biology Reports.

[3]  Hou-qun Ying,et al.  Relationship of SNP of H2BFWT gene to male infertility in a Chinese population with idiopathic spermatogenesis impairment , 2012, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[4]  Yingsong Wu,et al.  [Association of PRM1-190C- > A polymorphism with teratozoospermia]. , 2012, Zhonghua nan ke xue = National journal of andrology.

[5]  A. Giwercman,et al.  Polymorphisms, haplotypes and mutations in the protamine 1 and 2 genes. , 2011, International journal of andrology.

[6]  E. Nieschlag,et al.  A common haplotype of protamine 1 and 2 genes is associated with higher sperm counts. , 2010, International journal of andrology.

[7]  H. Rouba,et al.  Mutations in the protamine locus: association with spermatogenic failure? , 2009, Molecular human reproduction.

[8]  G D Adamson,et al.  International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) revised glossary of ART terminology, 2009. , 2009, Fertility and sterility.

[9]  S. de Mateo,et al.  A common protamine 1 promoter polymorphism (-190 C->A) correlates with abnormal sperm morphology and increased protamine P1/P2 ratio in infertile patients. , 2008, Journal of andrology.

[10]  A. Dumaine,et al.  Mutations in the protamine 1 gene associated with male infertility. , 2007, Molecular human reproduction.

[11]  D. Carrell,et al.  Altered protamine expression and diminished spermatogenesis: what is the link? , 2007, Human reproduction update.

[12]  C. Foresta,et al.  Genetic causes of male infertility. , 2006, Reproductive toxicology.

[13]  N. Hud,et al.  Formation of Native-like Mammalian Sperm Cell Chromatin with Folded Bull Protamine* , 2004, Journal of Biological Chemistry.

[14]  Barbara Sotolongo,et al.  Ability of Hamster Spermatozoa to Digest Their Own DNA1 , 2003, Biology of reproduction.

[15]  J. Ballescà,et al.  Marked differences in protamine content and P1/P2 ratios in sperm cells from percoll fractions between patients and controls. , 2003, Journal of andrology.

[16]  J. Ausió,et al.  A walk though vertebrate and invertebrate protamines , 2003, Chromosoma.

[17]  Y. Nishimune,et al.  Single nucleotide polymorphisms in the protamine-1 and -2 genes of fertile and infertile human male populations. , 2003, Molecular human reproduction.

[18]  C. Bertolotto,et al.  Cleavage of the Serum Response Factor during Death Receptor-induced Apoptosis Results in an Inhibition of the c-FOS Promoter Transcriptional Activity* , 2000, The Journal of Biological Chemistry.

[19]  P. J. Rowe,et al.  WHO Manual for the Standardized Investigation and Diagnosis of the Infertile Couple , 1993 .

[20]  J. Retief,et al.  Evolution of protamine P1 genes in primates , 1993, Journal of Molecular Evolution.

[21]  A. Fernandez,et al.  Serum response factor p67SRF is expressed and required during myogenic differentiation of both mouse C2 and rat L6 muscle cell lines , 1992, The Journal of cell biology.

[22]  R. Oliva,et al.  Vertebrate protamine gene evolution I. Sequence alignments and gene structure , 1990, Journal of Molecular Evolution.

[23]  Organización Mundial de la Salud.  WHO laboratory manual for the examination and processing of human semen , 2010 .

[24]  J. Auger,et al.  WHO laboratory manual for the examination and processing of human semen , 2010 .

[25]  S. Abid,et al.  Clinical and laboratory evaluation of idiopathic male infertility in a secondary referral center in India , 2008, Journal of clinical laboratory analysis.

[26]  C. Wadelius.  Genetic causes of male infertility. , 1998 .