P-91: Androgen Associated Gene Polymorphism(s) in Women with Polycystic Ovary Syndrome from South Indian Population

Background: Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder affecting 4-12% of reproductive women worldwide; characterized by chronic anovulation, clinical and/or biochemical hyperandrogenism, and polycystic ovaries on ultrasound scan. Ovarian androgen overproduction is the key pathophysiologic feature of PCOS. A number of genes encoding major enzymes of the androgen metabolic pathways have been examined and associations reported, however, these associations have not been unanimous. The CYP19 gene encodes aromatase (P450 arom) is a key steroidogenic enzyme that catalyzes the estrogen biosynthesis by converting testosterone and androstenedione to estradiol and estrone separately. Several polymorphisms of CYP19 gene were associated with variation in serum androgen concentrations among women. SNP rs2414096 in the CYP19 gene is linked with hyperandrogenism. The androgen effect at the molecular level is mediated through activation of androgen receptor (AR). A (CAG)n repeat polymorphism in exon 1 of the AR gene influences the transactivation of the receptor, resulting variation in androgen activity that could be related to a number of clinical conditions. Variation in the AR (CAG)n repeat may serve as a risk factor for the conditions sensitive to androgen levels. In view of the evidence implicating the importance of AR (CAG)n and CYP19 SNP rs2414096 in androgen metabolic pathways, we aimed to investigate the possible interactive role of the AR and CYP 19 genes in the phenotypic expression of PCOS in Indian women. Materials and Methods: The study was carried out in 346 individuals comprising of 189 patients and 157 normal women as controls. Samples were obtained from Modern Government Hospital, Hyderabad, India after obtaining institional ethical committee (Osmania University). DNA was isolated and ARMS PCR was performed by designing tetra primers for cyp19 rs2414096 and flanking primers for CAG repeats in exon-1of AR gene. Products were analysed using 2% agarose and 10% polyacrylamide gel for both the genes respectively. Results: Results showed 4%, 89%, 7% of AA, AG, GG genotypes in patients and 10%, 82%, and 9% in controls respectively. AA genotype was significantly elevated in the control group compared to patients suggesting protective role of this genotype to PCOS (p<0.05). The CAG repeat number varied between 13-27 with a mode of 22 repeats in controls. Individuals with <22 repeats were higher in patient group compared to the controls (70% vs 56%). When gene interaction was considered, GG with <22 CAG repeats has emerged out as the highly susceptible combination for PCOS. Further, genotypes in relation to various clinical features (Hirsutism, acanthosis, alopecia, acne) and anthropometric measures (BMI, W/H) were analysis using Logistic regression analysis. The susceptible genotype showed significant influence on some of these features. Conclusion: The findings of the present study support an interactive role of CYP 19 and AR gene variants in the hyperandrogenic phenotype of PCOS.