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

To examine the prevalence and the effects of Gly972Arg (G972A) variant of insulin receptor substrate-1 (IRS-1) in women with polycystic ovary syndrome (PCOS). Controlled clinical study. An academic clinical research center. Sixty women with PCOS and 60 control women matched for age. Biometric measures, metabolic and hormonal measures, genetic analyses. Serum androgens, glucose, and insulin were measured. Blood leukocytes were used for genetic analyses. 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. 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.