Insulin Resistance Is Attenuated in Women with Polycystic Ovary Syndrome with the ProAla Polymorphism in the PPAR Gene

Polycystic ovary syndrome (PCOS) is common in women of reproductive age and is associated with a high risk for development of type 2 diabetes. Insulin resistance, a key component in the pathogenesis of PCOS and glucose intolerance, is ameliorated by the thiazolidinediones, synthetic ligands for the PPAR . In the present study we have examined the relationship of the ProAla polymorphism in the PPAR gene (PPARG) to clinical and hormonal features of PCOS. Two hundred and eighteen women with PCOS had a 75-g oral glucose tolerance test, and blood was obtained for measurement of serum androgen levels. Sixty percent of the subjects were Caucasian, 26% were African-American, 6% were Hispanic, 6% were South Asian, and 2% were Middle-Eastern. Compared with Caucasians, the African-American group had a higher prevalence of diabetes (19% vs. 5%, respectively), were more obese (body mass index, 40.9 1.8 vs. 36.3 0.8 kg/m; P < 0.05), and were more insulin resistant. Twenty-eight of 218 subjects had the Ala allele, all in the heterozygous state. The frequency of the Ala allele varied among the groups: 0.01 in African-Americans, 0.08 in Caucasians, and 0.15 in Hispanics. Nondiabetic Caucasians with an Ala allele (Pro/Ala group) were more insulin sensitive than those in the Pro/Pro group, as evidenced by a lower homeostasis model assessment index (5.18 1.33 vs. 6.54 0.54; P < 0.05) and lower levels of insulin at both the fasting (132 27 vs. 165 12 pmol/liter; P 0.03) and 2 h (688 103 vs. 10190 99 pmol/liter; P 0.04) time points during the oral glucose tolerance test. We conclude that ProAla in PPARG is a modifier of insulin resistance in Caucasian women with PCOS. (J Clin Endocrinol Metab 87: 772–775, 2002)