FTO and MC4R Gene Variants Are Associated with Obesity in Polycystic Ovary Syndrome
Open Access
- 20 January 2011
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 6 (1), e16390
- https://doi.org/10.1371/journal.pone.0016390
Abstract
Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility in women. It is also associated with metabolic disturbances that place women at increased risk for obesity and type 2 diabetes. There is strong evidence for familial clustering of PCOS and a genetic predisposition. However, the gene(s) responsible for the PCOS phenotypes have not been elucidated. This two-phase family-based and case-control genetic study was designed to address the question of whether SNPs identified as susceptibility loci for obesity in genome-wide association studies (GWAS) are also associated with PCOS and elevated BMI. Members of 439 families having at least one offspring with PCOS were genotyped for 15 SNPs previously shown to be associated with obesity. Linkage and association with PCOS was assessed using the transmission/disequilibrium test (TDT). These SNPs were also analyzed in an independent case-control study involving 395 women with PCOS and 176 healthy women with regular menstrual cycles. Only one of these 15 SNPs (rs2815752 in NEGR1) was found to have a nominally significant association with PCOS (χ2 = 6.11, P = 0.013), but this association failed to replicate in the case-control study. While not associated with PCOS itself, five SNPs in FTO and two in MC4R were associated with BMI as assessed with a quantitative-TDT analysis, several of which replicated association with BMI in the case-control cohort. These findings demonstrate that certain SNPs associated with obesity contribute to elevated BMI in PCOS, but do not appear to play a major role in PCOS per se. These findings support the notion that PCOS phenotypes are a consequence of an oligogenic/polygenic mechanism.This publication has 32 references indexed in Scilit:
- Family-Based Analysis of Candidate Genes for Polycystic Ovary SyndromeJournal of Clinical Endocrinology & Metabolism, 2010
- Large effects on body mass index and insulin resistance of fat mass and obesity associated gene (FTO) variants in patients with polycystic ovary syndrome (PCOS)BMC Medical Genetics, 2010
- Evidence for Association between Polycystic Ovary Syndrome (PCOS) andTCF7L2and Glucose Intolerance in Women with PCOS andTCF7L2Journal of Clinical Endocrinology & Metabolism, 2009
- Replication and extension of genome-wide association study results for obesity in 4923 adults from northern SwedenHuman Molecular Genetics, 2009
- Six new loci associated with body mass index highlight a neuronal influence on body weight regulationNature Genetics, 2008
- Functional genetic polymorphisms and female reproductive disorders: Part I: polycystic ovary syndrome and ovarian responseHuman Reproduction Update, 2008
- Common variants near MC4R are associated with fat mass, weight and risk of obesityNature Genetics, 2008
- Genome-Wide Association Scan Shows Genetic Variants in the FTO Gene Are Associated with Obesity-Related TraitsPLoS Genetics, 2007
- Variation in FTO contributes to childhood obesity and severe adult obesityNature Genetics, 2007
- The role of proopiomelanocortin (POMC) neurones in feeding behaviourNutrition & Metabolism, 2007