Association of Gly972Arg variant of insulin receptor substrate-1 with metabolic features in women with polycystic ovary syndrome

Objective: To examine the prevalence and the effects of Gly972Arg (G972A) variant of insulin receptor substrate-1 (IRS-1) in woman with polycistic ovary syndrome (PCOS). Design: Controlled clinical study. Setting: An academic clinical research center. Patient(s): Sixty women with PCOS and 60 control women matched for age. Intervention(s): Biometric measures, metabolic and hormonal measures, genetic analyses. Main Outcome Measures(s): Serum androgens, glucose, and insulin were measured. Blood leukocytes were used for genetic analyses. Result(s): The G972A variant was encountered more often in women with PCOS The G972A carriers were more obese than their counterparts, had higher fasting insulin levels, and were more insulin-resistant. However androgen levels did not differ on the basis of IRS-1 genotype. Conclusion(s): We observed that the G972A variant of IRS-1 was more prevalent in women with PCOS, and that it had important metabolic effects without having a direct effect on the androgen levels. However, the G972A variant of IRS-1 may modulate reproduction by lowering sex hormone-binding globulin in both healthy women and women with PCOS.