P-205: Analysis of Mlh3 C2531T Polymorphism in Iranian Women with Unexplained Infertility

Background: Infertility is increasingly recognized as a major health problem. Meiotic genes are very important candidates for genes contributing to female and male infertility. Mammalian MutL homologues have dual roles in DNA mismatch repair (MMR) after replication errors and meiotic reciprocal recombination. There are four MutL homologues in eukaryotes that mutations of three of them (Mlh1, Mlh3, and Pms2) result in meiotic defects. Previous studies demonstrated that male and female Mlh3-deficient mice mated normally but were infertile. In female mice Mlh3-/- oocytes showed abnormalities in extrusion of the first and second polar bodies after in vitro fertilization with normal sperms of wild type mice, .The MutL homologs, Mlh1 and Mlh3, are crucial for meiotic reciprocal recombination. In our current study, we show that common SNP C2531T in the Mlh3 gene is associated with unexplained infertility in Iranian women. Materials and Methods: We investigated Iranian patients, including 105 women with unexplained infertility and 100 women with at least one child and no history of infertility or abortion as controls. Results: Genotypes CC, CT and TT of the Mlh3gene presented frequencies of 4.76%,77.15% and 18.1%, respectively, in the women with unexplained infertility and 25%,73% and 2% in the controls (p<0.001). Conclusion: The data suggest that the Mlh3 C2531T polymorphism can be associated with risk of female infertility and presence of the polymorphic allele T leads to an increased risk of 2.09 times (OR =2.09, 95% CI =1.38-3.16; p<0.001) to develop infertility in relation to the control group.