CYP19 gene: a genetic modifier of polycystic ovary syndrome phenotype

Objective: To evaluate the possible contribution of the (TTTA)n polymorphism of aromatase gene (CYP19) to the hyperandrogenic phenotype of polycystic ovary syndrome (PCOS). Design: Case-control study. Setting: Endocrine outpatients' clinic of a tertiary university hospital. Patient(s): One hundred eighty women with PCOS and 160 healthy controls of reproductive age. Intervention(s): Blood sampling for genotype analysis, and measurement of androgens, E-2, LH, FSH, and fasting glucose and insulin. Main Outcome Measure(s): Frequency of the CYP19(TTTA)n polymorphism and association with hormone concentrations. Result(s): Women with PCOS tended to have more frequently short (TTTA)n alleles (with nine or fewer repeats) than healthy controls (33.1% vs. 29.5%), although the difference was not statistically significant. However, patients in the highest quartile for serum T were more frequently homozygous for short alleles compared with controls (59.1% vs. 42.1%) and patients in lower quartiles (59.1% vs. 36.9%). Furthermore, the patients homozygous for short alleles had higher T/E-2 ratios, higher T levels, and higher LH/FSH ratios compared with those with longer alleles. Conclusion(s): Although CYP19 may not be a major genetic determinant of PCOS, it may act as a genetic modifier of the hyperandrogenic phenotype of PCOS. The presence of short CYP19(TTTA)n alleles may contribute to prenatal androgenization programming the development of PCOS phenotype in adult life. (Fertil Steril (R) 2010; 94: 250-4. (C) 2010 by American Society for Reproductive Medicine.)