Variation in Resistin Gene Promoter Not Associated With Polycystic Ovary Syndrome Margrit Urbanek 1 , Yangzhu Du 1 , Kaisa Silander 2 , Francis S. Collins 2 , Claire M. Steppan 3 , Jerome F. Strauss III 4 , Andrea Dunaif 5 , Richard S. Spielman 1 and Richard S. Legro 6 1 Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 2 Genome Technology Branch, National Human Genome Research Institute, Bethesda, Maryland 3 Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 4 Center for Research on Reproduction and Women’s Health and Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 5 Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Medical School, Chicago, Illinois 6 Department of Obstetrics and Gynecology, College of Medicine, Pennsylvania State University, Hershey, Pennsylvania Abstract Polycystic ovary syndrome (PCOS) is a leading cause of anovulatory infertility and affects ∼4–7% of reproductive age women in the U.S. It is characterized by hyperandrogenemia and chronic anovulation and is associated with insulin resistance, obesity, and increased risk for type 2 diabetes. In a screen of candidate genes, a region on chromosome 19p13.3 was identified that shows significant evidence for both linkage and association with PCOS. A promising candidate gene for PCOS, resistin, maps to exactly this region. Resistin is a protein hormone thought to modulate glucose tolerance and insulin action. We tested for association between a single nucleotide polymorphism in the promoter region of the resistin gene and three phenotypes: PCOS, obesity, and insulin resistance. We did not find evidence for association with any of the phenotypes. It is therefore unlikely that variation in the resistin gene accounts for the strong association that we observe between chromosome 19p13.3 and PCOS. Instead, this association is most likely due to a gene or genetic element in this region that has not been identified. Footnotes Address correspondence and reprint requests to Richard S. Spielman, Department of Genetics, Clinical Research Building, University of Pennsylvania School of Medicine, 415 Curie Blvd., Philadelphia, PA 19104-6145. E-mail: spielman{at}pobox.upenn.edu . Received for publication 7 June 2002 and accepted in revised form 14 October 2002. M.U. is currently located at the Department of Medicine, Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Medical School, Chicago, Illinois. HA, hyperandrogenemia; PCOS, polycystic ovary syndrome; PPARγ, peroxisome proliferator–activated receptor-γ; SNP, single nucleotide polymorphism; TDT, transmission/disequilibrium test. DIABETES