Association Between Semen Paraoxonase-۱ Activity Level and L۵۵M Gene Variants with Risk of Male Infertility

Today evaluation of polymorphisms of the antioxidant enzyme-encoding genes, which affect the activity of antioxidant enzymes, could be used as risk prediction models for male infertility. This study aims to evaluate coloration of serum paraoxonase (PON۱) activity levels in the semen and its L۵۵M gene variants with risk male infertility. In a case-control study, semen samples were collected from ۸۰ healthy controls and ۱۲۸ infertile men at Fatemeh Al-Zahra IVF and Pastor Laboratory (Babol, Mazandaran, Iran). PON۱ activity of semen samples was measured by spectrophotometric methods. Genotyping of all individuals based on PON۱-L۵۵M loci performed by PCR-RFLP and PCR-sequencing and molecular effects of leucine (L) to methionine (M) substitution were investigated by bioinformatics tools. Results showed a significant difference in genotype frequencies of PON۱-L۵۵M polymorphism between patient and control groups, and c.۱۶۳T>A transition effect on the structure and function of PON۱ protein. Also, TA genotype (OR=۱.۷۵۴, ۹۵%CI=۰.۹۷۱ to ۳.۱۶۶, P= ۰.۰۶۲) and AA genotype (OR=۵.۰۶۷, ۹۵%CI=۱.۳۶۶ to ۱۸.۷۸۹, P= ۰.۰۱۵) were associated with male infertility. Men with mutant allele (AA+TA) are exposed to be at the risk of male infertility (OR= ۱.۹۹۰, ۹۵%CI= ۱.۱۱۸ to ۳.۵۴, P= ۰.۰۱۹). Also, the allelic analysis showed that the A allele was associated with the increased risk of idiopathic male infertility (OR= ۱.۷۴۹, ۹۵%CI= ۱.۱۴۳ to ۲.۶۷۶, P= ۰.۰۱۰). Additionally, PON۱ activity was higher in the TT (LL) individuals compared to the TA (LM) and AA (MM) men in both groups (LL> LM> MM). Since, the PON۱-L۵۵M gene variants are related to PON۱ activity levels in the semen and serum paraoxonase is known as an important antioxidant calcium-dependent enzyme, it could be implicated in male infertility. Based on these findings, the presence of mutant allele (A) and or decreasing semen’s PON۱ level may be an indicator/ prediction factor for male infertility.

کلیدواژه ها:

Male infertility ، Oxidative stress ، PON۱-L۵۵M ، Semen paraoxonase۱