Assessment of Vitamin D Receptor Gene Polymorphism in Iraqi Women with Polycystic Ovary Syndrome

Abstract

Introduction: Polycystic Ovary Syndrome (PCOS) is the most common hormonal disorder in women that occurs mainly in the reproductive age. It is suggested to be highly complex and heterogeneous disorder with an uncertain cause. Genes included in vitamin D metabolism have been assumed as candidate genes for the PCOS susceptibility. Vitamin D receptor gene polymorphisms are suggested to have an influential role in insulin metabolism in women with PCOS. Aim: To investigate the possible association between Cdx2 (G/A) Single Nucleotide Polymorphism (SNP) of vitamin D receptor gene and the risk of polycystic ovary syndrome. Materials and Methods: The present Case-control study involved 88 women from 18 to 34 years of age in which Group 1 consisted of 45 newly diagnosed women with PCOS while Group 2 consisted of 43 women without PCOS that acted as controls. DNA samples were amplified and analysed for the Cdx2 (G/A) SNP of vitamin D receptor gene. Genotypic frequency distribution of Cdx2 polymorphism of vitamin D receptor gene was calculated in women with PCOS and controls. From each serum sample 25-hydroxy vitamin D, calcium, LH, FSH, free testosterone, insulin, and glucose was calculated according to AA, GA, and GG genotypic distribution. Results: There was no significant difference in genotypic distributions of Cdx2 polymorphism of vitamin D receptor gene between patients and controls. In addition, the results of patients group were found to be significantly lower for fasting serum glucose (p=0.02), insulin (p=0.01), and Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) (p<0.001) inindividuals with AA genotype than individual with GA and GG genotype. While, significantly higher levels of LH (p=0.002) and LH/FSH ratio (p=0.003) inindividual with GG genotype than individual with GA and AA genotype, and no significant difference in mean value of FSH (p=0.148) and free testosterone (p=0.091) between GG, GA, and AA carriers. Likewise, the results were observed significantly lower levels for serum 25-hydroxy vitamin D in GG carriers than GA and AA carriers for both patients (p<0.001) and controls (p<0.001), with no significant difference in mean value of calcium levels between GG, GA and AA carriers for patients (p=0.949) and controls (p=0.46). Conclusion: Cdx2 polymorphism of vitamin D receptor gene has an association with severity of clinical features in PCOS; however, not with risk of development of the disease meaning that genetic variation is not directly linked to risk of this syndrome but may indirectly affect disease development via regulation of vitamin D levels.

Keywords

• cdx2 polymorphism
• hormonal disorder
• single nucleotide polymorphism