Polymorphism of the follistatin gene in polycystic ovary syndrome.

Follistatin has been reported as a candidate gene for polycystic ovary syndrome (PCOS) from linkage and association studies. Acting to regulate the development of ovarian follicles and as an antagonist to aromatase activity, alterations in follistatin function or expression may result in key features of PCOS such as reduced serum FSH, impaired ovarian follicle development and augmented ovarian androgen production. We investigated polymorphisms in the FST gene to determine if genetic variation is associated with susceptibility to PCOS or key phenotypic features of PCOS patients in a case-control association study. One hundred and seventy-three PCOS patients of Caucasian descent (mean age 30.0 +/- 4.8 years), conforming to the NIH diagnostic criteria, were recruited from a clinical practice database and 107 normal ovulating women (mean age 38.8 +/- 13.4 years) were recruited from the general community as control subjects. Morphometric data, biochemistry and genomic DNA were collected from study subjects and genotyping was performed on seven Single nucleotide polymorphisms (SNPs) in the FST gene region. Allele frequencies of the SNPs were rs1423560 G/C (0.99/0.01), rs3797297 C/A (0.80/0.20), rs11745088 C/G (0.98/0.02), rs3203788 A/T (0.98/0.02) and rs1062809 G/C (1.00/-), rs1127760 A/T (0.98/0.02) and rs1127761 A/T (0.98/0.02), and these were not significantly different between the PCOS and control groups (P < 0.05). Statistical analysis revealed significant associations between the SNP rs3797297 and sex hormone-binding globulin (P = 0.04) and free androgen index (FAI) (P < 0.01). We conclude that FST is not a susceptibility locus for PCOS; however, the SNP rs3797297 from FST gene was associated with androgenic markers for PCOS and may be of importance in the hyperandrogenaemia of the disease.