Microsatellite polymorphism (tttta)n at-528 base pairs of gene CYP11α influences hyperandrogenemia in patients with polycystic ovary syndrome

Objective: To investigate the functional significance of CYP11 alpha microsatellite polymorphism (tttta)(n) (-528 base pairs) in patients with polycystic ovary syndrome. Design: Follow-up study. Setting: Academic research center. Patient(s): Eighty patients and 90 controls. Intervention(s): Body mass indices and waist-to-hip ratios were determined. Blood samples were obtained for DNA analysis and hormone measurements. Main Outcome Measure(s): CYP11 alpha marker (tttta), genotyping and serum total testosterone levels. Result(s): All the women were assigned to one of two genotype groups: 216+ (for women who had at least one copy of high frequency allele 216 with four repeat units) or 216- (for women who did not have allele 216). Fifty-nine patients (73.75%) had genotype 216+; their mean (+/- SD) total testosterone level was 78.0 +/- 19.8 ng/dL. Twenty-one patients (26.25%) had genotype 216-; their mean (+/-SD) total testosterone level was 100.0 +/- 23.3 ng/dL. The difference in total testosterone levels was statistically significant. Seventy-eight controls (86.67%) had genotype 216+ and 12 controls (13.33%) had genotype 216-, the total testosterone levels of these two groups were similar (38.6 +/- 15.5 vs. 40.3 +/- 12.1 ng/dL). The difference in genotype distribution between the women with polycystic ovary syndrome and the controls (26.25% vs. 13.33% with genotype 216-) was statistically significant. Conclusion(s): CYP11 alpha (tttta)(n) allelic variants were associated with both polycystic ovary syndrome and total testosterone levels in women with polycystic ovary syndrome, suggesting the existence of an epistasis phenomenon.