Polymorphism T --> C (-34 base pairs) of gene CYP17 promoter in women with polycystic ovary syndrome is associated with increased body weight and insulin resistance: a preliminary study.

The aim of this study was to establish the frequency of gene CYP17 promoter polymorphism in women with polycystic ovary syndrome (PCOS) from a Chilean population and to examine the association of this polymorphism with body weight and estimate of insulin resistance in PCOS patient carriers and noncarriers of the A2 allelic variant. A total of 159 women with clinical and hormonal evidence of PCOS and 93 healthy women (HW) were evaluated. Diagnosis of PCOS was made according to the National Institutes of Health consensus criteria. In PCOS and HW, an oral glucose tolerance test was performed; and serum glucose and insulin were measured before the glucose load and 30, 60, 90, and 120 minutes after. Lipid profile and free fatty acid concentrations were determined in the basal sample. Insulin resistance was evaluated by homeostatic model assessment and insulin sensitivity index composite. A polymerase chain reaction-restriction fragment length polymorphism analysis was performed in all women to determine the A2 allele of the gene CYP17 promoter. The genotype frequency was similar between HW and PCOS women. No differences in anthropometric measurements and metabolic parameters were observed in HW carrier and noncarrier of the A2 variant. In PCOS women, an increase in body mass index, waist circumference, homeostatic model assessment of insulin resistance, and fasting insulin according to the A2 allele dosage was observed (P = .008, P = .016, P = .012, and P = .006, respectively). Polycystic ovary syndrome patient carriers of the A2 allele with a body mass index greater than 29.9 kg/m(2) showed an odds ratio of 9.1 (confidence interval, 3.0-27.4; P < .0001) for developing insulin resistance. These data suggest that the frequency of the A2 allele is similar between PCOS patients and HW; however, the presence of this gene defect in PCOS patients seems to be associated with increase in body weight, abdominal adiposity, and metabolic components.