Association between The SIRT1 and SIRT3 Levels and Gene Polymorphisms with Infertility in War Zones of Kermanshah Province, Iran: A Case-Control Study.

Abstract

War toxin, mustard gas, alkylating agent results in male infertility via inducing reactive oxygen species (ROS) production and DNA mutagenesis. SIRT1 and SIRT3 are multifunctional enzymes that involve in the DNA repair, oxidative stress responses. This study aim is to assess the correlation between serum levels of SIRT1, SIRT3 and both rs3758391T>C and rs185277566C>G gene polymorphisms with infertility in the war zones of Kermanshah province, Iran. In this case-control study based on the semen analysis, samples were divided into two groups infertile (n=100) and fertile (n=100). High-performance liquid chromatography (HPLC) method was used to determine the malondialdehyde level, and also a sperm chromatin dispersion (SCD) test was used to evaluate the DNA fragmentation rate. Using the colorimetric assays, superoxide dismutase (SOD) activity was measured. SIRT1 and SIRT3 protein levels were determined by using ELISA. The genetic variants of SIRT1 rs3758391T>C, and SIRT3 rs185277566C>G, were detected by polymerase chain reaction-restriction fragment length (PCR-RFLP) technique. Malondialdehyde (MDA) level and the percentage of DNA fragmentation were higher in infertile samples, but serum levels of SIRT1 and SIRT3, and SOD activity was lower in infertile compared to fertile samples (P<0.001). The TC+CC genotypes and the C allele from SIRT1 rs3758391T>C polymorphism, and CG+GG genotypes and the G allele from SIRT3 rs185277566C>G polymorphism could increase risk of infertility (P<0.05). The results of this study suggest that war toxins through the impact on genotypes, decreasing levels of SIRT1 and SIRT3 and increasing levels of oxidative stress, lead to defects in the concentration, motility and morphology of sperms and thus, infertility in men.