Gly1057Asp Polymorphism of the Insulin Receptor Substrate-2 Genes May Not Have a Significant Impact on Insulin Resistance in Korean Women with Polycystic Ovary Syndrome

Abstract

Background: Insulin resistance is a key factor in the pathogenesis of polycystic ovary syndrome (PCOS), and several candidate genes involved in insulin action such as insulin receptor or insulin recpetor substrate (IRS) have been investigated. In this study, we examined the genetic effects of the IRS-1 and IRS-2 genes on the metabolic and reproductive features in women with PCOS. Methods: 125 patients with PCOS and 344 regular cycling controls were enrolled. Analysis of the polymorphisms of Gly972Arg in the IRS-1 gene and Gly1057Asp in the IRS-2 gene was performed and oral glucose tolerance tests and hyperinsulinemic euglycemic clamp tests were done. Results: The genotype frequencies of the Gly972Arg polymorphism in the IRS-1 gene and the Gly1057Asp polymorphism in the IRS-2 gene were not significantly different between the women with PCOS and the controls. Gly972Arg polymorphism of the IRS-1 gene was extremely rare in both groups. PCOS women with the IRS-2 Asp1057Asp genotype showed significantly higher hirsutism scores, higher levels of free testosterone and higher post-load 60, 90, and 120 min plasma glucose levels compared to those women with the Gly1057Gly or Gly1057Asp genotype. In contrast, the control women with the Asp1057Asp genotype showed significantly lower post-load 60, 90, and 120 min plasma glucose levels compared with those women with the Gly1057Gly or Gly1057Asp genotype. Conclusion: Gly972Arg polymorphism of the IRS-1 gene was extremely rare in Korean women. Gly1057Asp polymorphism of the IRS-2 gene was associated with the phenotypic features of PCOS such as hirsutism, hyperandrogenemia and hyperglycemia, but it was not associated with the insulin sensitivity index. In conclusion, Gly1057Asp polymorphism of the IRS-2 gene may not have a significant impact on insulin resistance in Korean women with PCOS. (J Korean Endocr Soc 24:100~108, 2009) ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ