VDR gene polymorphisms as a significant factor in unexplained infertility

Objectives: There are various cellular and molecular disorders of the endometrium that have been associated with unexplained infertility (UI). The physiological effects of 1,25(OH)(2)D-3 are directed by the nuclear Vitamin D receptor(VDR). VDR gene expression and vitamin D converting enzyme have been displayed in both the proliferative and secretory process of the menstrual period in the endometrium. The study demonstrated the defects of uterine development and decidualization resulting in infertility in the VDR knockout of female mice. Design & methods: VDR gene polymorphisms and vitamin D levels were studied in the groups, included 101 patients and 100 control, by the PCR-RFLP and the method of ECLIA. Our findings suggest that the VDR gene polymorphisms are connected with the risk of UI and, interestingly, genotypes were associated with vitamin D because serum vitamin D levels were importantly greater with Aa, Bb, TT, FF, and ff genotypes in the UI group (p = 0.001*, p = 0.001*, p = 0.002*, p = 0.004*, p = 0.003*, respectively). We showed that having the Aa genotype in VDR gene ApaI polymorphism reduced the risk of UI by 80% (p = 0.044, OR = 0.20, CI: [0.04-0.96]); having the Tt, tt genotypes in VDR gene TaqI polymorphism increased the risk of UI by 4.26 times (p = 0.001 OR = 4.26, CI:[2.10-8.62])and, 4.32 times (p = 0.001, OR = 4.32, CI:[1.76-10.62]), respectively; and having the BB genotype in BsmI polymorphism increased the risk of UI by 3.47 times (p = 0.005, OR = 3.47, CI:[1.44-8.36]). Conclusion: As a consequence, impaired VDR gene expression affects the endometrial receptivity and the success of the implantation via unknown mechanisms.