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

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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.

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Authors and Affiliations

  1. Genetic Division, Department of Biology, School of Sciences, Islamic Azad University of Ashkezar, Yazd, Iran

    Shirin Jamali

  2. Gametogenesis Research Center, Kashan University of Medical Sciences, Kashan, Iran

    Mohammad Karimian & Hossein Nikzad

  3. Anatomical Sciences Research Center, Kashan University of Medical Sciences, Kashan, Iran

    Hossein Nikzad

  4. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Younes Aftabi

  5. Molecular and Cell Biology Department, Faculty of Basic Sciences, University of Mazandaran, Babolsar, Iran

    Mohammad Karimian & Younes Aftabi

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  1. Shirin Jamali
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  4. Younes Aftabi
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Correspondence to Hossein Nikzad.

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11033_2016_4017_MOESM1_ESM.tif

Supplementary material 1 (TIFF 705 kb) Fig. S1 ASSP prediction results. Splice sites prediction when nucleotide G locates in the position 298 (A); Splice sites after C substitution in the 298 (B)

11033_2016_4017_MOESM2_ESM.tif

Supplementary material 2 (TIFF 290 kb) Fig. S2 NetGene2 prediction results: Splice sites prediction in the case of nucleotide G locates in the position 298 (A); Splice sites pattern after C substitution in the 298 (B). CUTOFF values used for confidence: Highly confident donor sites (H):95.0 %; Nearly all true donor sites: 50.0 %; Highly confident acceptor sites (H):95.0 %; nearly all true acceptor sites: 20.0 %

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Jamali, S., Karimian, M., Nikzad, H. et al. The c.−190 C>A transversion in promoter region of protamine1 gene as a genetic risk factor for idiopathic oligozoospermia. Mol Biol Rep 43, 795–802 (2016). https://doi.org/10.1007/s11033-016-4017-8

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  • DOI: https://doi.org/10.1007/s11033-016-4017-8

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