Introduction: Insulin resistance is a main characteristic of polycystic ovary syndrome (PCOS) and contributes to the increased risk of type 2 diabetes and cardiovascular disease. It is thought that in PCOS there is an alteration in the insulin signaling pathway. An important kinase in this pathway is the phosphatidylinositol 3 kinase (PI3K), the activity of which has been found to be decreased in PCOS. Based on this observation we investigated whether a single nucleotide polymorphism (rs1043526, A>G) of PIK3R1 gene that encodes the phosphatidylinositol 3 kinase regulatory subunit 1 (p85a) is involved in PCOS. This polymorphism is located in the 3′-UTR of PIK3R1 gene, where miRNAs can bind and thus regulate gene expression.
Subjects and methods: We studied 68 women with PCOS and 136 healthy women of reproductive age. Both patients and controls had normal weight. Hormonal profile was determined on 35th day of menstrual cycle. Insulin resistance was assessed by fasting glucose to insulin ratio and HOMA index. DNA was extracted from peripheral blood leucocytes and the rs1043526 polymorphism of PIK3R1 gene was genotyped. All subjects gave their consent and the local Ethical Committee approval was obtained.
Results: The PIK3R1 genotypes were found to be in Hardy-Weinberg equilibrium in both study groups (P>0.05). A significant difference was found in the distribution of rs1043526 genotypes between patients and controls. Women with PCOS had a greater frequency of AG and GG genotypes than normal women (35.3% vs 19.9%, P=0.016). Furthermore, among patients, those with AG and GG genotypes had higher fasting glucose levels compared to those with the AA genotype (90.1±6.1mg/dl vs 86.2±8.8 mg/dl, P=0.03). Also, a non significant increase was found in fasting insulin levels and insulin resistance indexes in women with AG and GG genotypes.
Conclusion: The rs1043526 A>G polymorphism of PIK3R1 gene may be involved in the pathogenesis of PCOS and affects glucose metabolism.