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Allelic Variants of the Follistatin Gene in Polycystic Ovary Syndrome¹

Department of Genetics (M.U., K.R.V., R.S.S.), and Center for Research on Reproduction and Women’s Health and Department of Obstetrics and Gynecology (L.-C.K., L.K.C., D.A.D., J.F.S.), University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104; Division of Women’s Health (X.W., A.D.), Brigham and Women’s Hospital, Boston, Massachusetts 02115; Reproductive Endocrine Unit (A.S.), Massachusetts General Hospital, Boston, Massachusetts 02114; and Department of Obstetrics and Gynecology (R.S.L.), Pennsylvania State University, College of Medicine, Hershey, Pennsylvania 17033

Address all correspondence and requests for reprints to: Margrit Urbanek, Department of Genetics, University of Pennsylvania, School of Medicine, 415 Curie Boulevard, Philadelphia, Pennsylvania 19104-6145. E-mail: murbanek{at}mail.upenn.edu

In an earlier study of 37 candidate genes for polycystic ovary syndrome (PCOS), the strongest evidence for genetic linkage was found with the region of the follistatin gene. We have now carried out studies to detect variation in the follistatin gene and assess its relevance to PCOS. By sequencing the gene in 85 members of 19 families of PCOS patients, we found sequence variants at 17 sites. Of these, 16 sites have variants that are too rare to make a major contribution to susceptibility; the only common variant is a single 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; messenger 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.

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