OBJECTIVE: 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). 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 MEASURE(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.
OBJECTIVE: 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). 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 MEASURE(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.