(249) Association of Single Nucleotide Polymorphisms (rs2301365 & Rs737008) in PRM1 Gene and Male Infertility: A Meta-Analysis

Abstract

Abstract Introduction In the sperm nucleus, protamine is a major DNA-binding protein that replaces histone. It is a basic arginine-rich protein responsible for DNA compaction. Protamin I (PRM1) is one of the important genes that produces protamine. Mutations and polymorphisms in PRM1 may increase the odds of male infertility. Objective The present meta-analysis investigated the association of single nucleotide polymorphisms (SNPs) (rs2301365 & rs737008) in the PRM1 gene and male infertility. Methods The original research articles, published till July 2023 in the English language, on the association of rs2301365 and rs737008 in the PRM1 gene and male infertility, were retrieved from Science Direct, PubMed, NCBI and Google Scholar. Results A total of 129 studies were retrieved by searching in the different databases, after the removal of duplicates, meta-analysis, and abstracts, 14 were finally selected. In 11 case-control studies, the association of the rs2301365 (-190C >A) polymorphism was presented as the meta-analysis of different models, Allelic model (C vs. A), Dominant model (CC + CA vs. AA), Recessive model (CC vs. CA + AA), Additive model (CC vs. AA), Heterozygous model (AC vs. AA). Allelic, additive, dominant and heterozygous models reported that the -190C>A (rs2301365) increased the odds of male infertility. The ethnic subgroup analysis showed the same pattern of association for the Caucasian infertile men. However, none of these overall and subgroup analyses based on ethnicity showed an association between rs2301365 (-190C >A) and infertility in Asian men. For rs737008 (139C > A) in the meta-analysis of 14 studies, none of these overall and subgroup analyses based on ethnicity showed an association with male infertility. Trial sequential analysis (TSA) for the allelic model of rs2301365 (-190C >A) showed the required sample size was 2252 at 90% power and 5% type-I error, whereas the cumulative z-curve crossed the trial sequential monitoring boundaries of harm. However, the sample size was greater than required therefore further studies will not likely change results. For rs737008 (139C > A), TSA recommended more studies to be conducted. Conclusions The PRM1 rs2301365 (-190C >A) was associated with male infertility in overall analysis and Caucasian men. Further studies on this SNP may not change results. However, rs737008 (139C > A) was not associated with male infertility. However, further studies are recommended. Disclosure No.