Allelic variants of the follistatin gene in polycystic ovary syndrome

In an earlier study of 37 candidate genes for polycystic ovary syndrome (PC OS), the strongest evidence for genetic linkage was found with the region o f the follistatin gene. We have now carried out studies to detect variation in the follistatin gene and assess its relevance to PCOS. By sequencing th e gene in 85 members of 19 families of PCOS patients, we found sequence var iants at 17 sites. Of these, 16 sites have variants that are too rare to ma ke a major contribution to susceptibility; the only common variant is a sin gle base pair change in the last exon at a site that is not translated, In our sample of 249 families, the evidence for linkage between PCOS and this variant is weak. We also examined the expression of the follistatin gene; m essenger RNA levels in cultured fibroblasts from PCOS and control women did not differ appreciably. We conclude that contributions to the etiology of PCOS from the follistatin gene, if any, are likely to be small.