Surabhi Bhatt1, Priscilla Mutharasan, Obed A Garcia, Nadereh Jafari, Richard S Legro, Andrea Dunaif, Margrit Urbanek. 1. Division of Endocrinology, Metabolism, and Molecular Medicine (S.B., P.M., O.A.G., A.D., M.U.) and Center for Genetic Medicine (N.J.), Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611; and Department of Obstetrics and Gynecology (R.S.L.), Pennsylvania State University, College of Medicine, Hershey, Pennsylvania 17033.
Abstract
CONTEXT: Although inflammation is clearly associated with obesity, diabetes, and insulin resistance, the role of chronic inflammation in the etiology of polycystic ovary syndrome (PCOS) is unclear. OBJECTIVE: To determine whether chronic inflammation plays a causal role in the etiology of PCOS, we tested for an association between PCOS and genetic markers mapping to 80 members of the inflammatory pathway. DESIGN: This was a case-control association study. SETTING: The setting was an academic medical center. PATIENTS OR PARTICIPANTS: A total of 905 index case patients with PCOS and 955 control women (108 intensively phenotyped subjects with normal androgen levels and regular menses and 847 minimally phenotyped subjects with regular menses and no history of PCOS). INTERVENTIONS: Subjects were genotyped at single nucleotide polymorphisms mapping to 80 inflammatory genes. Logistic regression was used to test for an association between 822 single nucleotide polymorphisms and PCOS after adjustment for population stratification, body mass index, and/or age. In the index patients, we also tested for association with 11 quantitative traits (body mass index and testosterone, fasting insulin, fasting glucose, 2-hour postchallenge glucose, LH, FSH, total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglyceride levels). MAIN OUTCOME MEASURES: The evidence for an association with PCOS and with 11 quantitative traits was investigated. RESULTS: Nominally significant evidence for an association was observed with MAP3K7, IKBKG, TNFRS11A, AKT2, IL6R, and IRF1, but no results remained statistically significant after adjustment for multiple testing. CONCLUSIONS: Genetic variation in the inflammatory pathway is not a major contributor to the etiology of PCOS or related quantitative traits in women with PCOS.
CONTEXT: Although inflammation is clearly associated with obesity, diabetes, and insulin resistance, the role of chronic inflammation in the etiology of polycystic ovary syndrome (PCOS) is unclear. OBJECTIVE: To determine whether chronic inflammation plays a causal role in the etiology of PCOS, we tested for an association between PCOS and genetic markers mapping to 80 members of the inflammatory pathway. DESIGN: This was a case-control association study. SETTING: The setting was an academic medical center. PATIENTS OR PARTICIPANTS: A total of 905 index case patients with PCOS and 955 control women (108 intensively phenotyped subjects with normal androgen levels and regular menses and 847 minimally phenotyped subjects with regular menses and no history of PCOS). INTERVENTIONS: Subjects were genotyped at single nucleotide polymorphisms mapping to 80 inflammatory genes. Logistic regression was used to test for an association between 822 single nucleotide polymorphisms and PCOS after adjustment for population stratification, body mass index, and/or age. In the index patients, we also tested for association with 11 quantitative traits (body mass index and testosterone, fasting insulin, fasting glucose, 2-hour postchallenge glucose, LH, FSH, total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglyceride levels). MAIN OUTCOME MEASURES: The evidence for an association with PCOS and with 11 quantitative traits was investigated. RESULTS: Nominally significant evidence for an association was observed with MAP3K7, IKBKG, TNFRS11A, AKT2, IL6R, and IRF1, but no results remained statistically significant after adjustment for multiple testing. CONCLUSIONS: Genetic variation in the inflammatory pathway is not a major contributor to the etiology of PCOS or related quantitative traits in women with PCOS.
Authors: Shaun Purcell; Benjamin Neale; Kathe Todd-Brown; Lori Thomas; Manuel A R Ferreira; David Bender; Julian Maller; Pamela Sklar; Paul I W de Bakker; Mark J Daly; Pak C Sham Journal: Am J Hum Genet Date: 2007-07-25 Impact factor: 11.025
Authors: John R B Perry; Michael N Weedon; Claudia Langenberg; Anne U Jackson; Valeriya Lyssenko; Thomas Sparsø; Gudmar Thorleifsson; Harald Grallert; Luigi Ferrucci; Marcello Maggio; Giuseppe Paolisso; Mark Walker; Colin N A Palmer; Felicity Payne; Elizabeth Young; Christian Herder; Narisu Narisu; Mario A Morken; Lori L Bonnycastle; Katharine R Owen; Beverley Shields; Beatrice Knight; Amanda Bennett; Christopher J Groves; Aimo Ruokonen; Marjo Riitta Jarvelin; Ewan Pearson; Laura Pascoe; Ele Ferrannini; Stefan R Bornstein; Heather M Stringham; Laura J Scott; Johanna Kuusisto; Peter Nilsson; Malin Neptin; Anette P Gjesing; Charlotta Pisinger; Torsten Lauritzen; Annelli Sandbaek; Mike Sampson; Ele Zeggini; Cecilia M Lindgren; Valgerdur Steinthorsdottir; Unnur Thorsteinsdottir; Torben Hansen; Peter Schwarz; Thomas Illig; Markku Laakso; Kari Stefansson; Andrew D Morris; Leif Groop; Oluf Pedersen; Michael Boehnke; Inês Barroso; Nicholas J Wareham; Andrew T Hattersley; Mark I McCarthy; Timothy M Frayling Journal: Hum Mol Genet Date: 2009-11-18 Impact factor: 6.150
Authors: Alkes L Price; Johannah Butler; Nick Patterson; Cristian Capelli; Vincenzo L Pascali; Francesca Scarnicci; Andres Ruiz-Linares; Leif Groop; Angelica A Saetta; Penelope Korkolopoulou; Uri Seligsohn; Alicja Waliszewska; Christine Schirmer; Kristin Ardlie; Alexis Ramos; James Nemesh; Lori Arbeitman; David B Goldstein; David Reich; Joel N Hirschhorn Journal: PLoS Genet Date: 2007-11-19 Impact factor: 5.917