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.