Impact of FTO genotypes on BMI and weight in polycystic ovary syndrome: a systematic review and meta-analysis
Year: 2012
Type: review
Study designs: Systematic Review, Meta-Analysis
Abstract: AIMS/HYPOTHESIS: FTO gene single nucleotide polymorphisms (SNPs) have been shown to be associated with obesity-related traits and type 2 diabetes. Several small studies have suggested a greater than expected effect of the FTO rs9939609 SNP on weight in polycystic ovary syndrome (PCOS). We therefore aimed to examine the impact of FTO genotype on BMI and weight in PCOS. METHODS: A systematic search of medical databases (PubMed, EMBASE and Cochrane CENTRAL) was conducted up to the end of April 2011. Seven studies describing eight distinct PCOS cohorts were retrieved; seven were genotyped for SNP rs9939609 and one for SNP rs1421085. The per allele effect on BMI and body weight increase was calculated and subjected to meta-analysis. RESULTS: A total of 2,548 women with PCOS were included in the study; 762 were TT homozygotes, 1,253 had an AT/CT genotype, and 533 were AA/CC homozygotes. Each additional copy of the effect allele (A/C) increased the BMI by a mean of 0.19 z score units (95% CI 0.13, 0.24; p = 2.26 × 10(-11)) and body weight by a mean of 0.20 z score units (95% CI 0.14, 0.26; p = 1.02 × 10(-10)). This translated into an approximately 3.3 kg/m(2) increase in BMI and an approximately 9.6 kg gain in body weight between TT and AA/CC homozygotes. The association between FTO genotypes and BMI was stronger in the cohorts with PCOS than in the general female populations from large genome-wide association studies. Deviation from an additive genetic model was observed in heavier populations. CONCLUSIONS/INTERPRETATION: The effect of FTO SNPs on obesity-related traits in PCOS seems to be more than two times greater than the effect found in large population-based studies. This suggests an interaction between FTO and the metabolic context or polygenic background of PCOS.
Source: Diabetologia
Authors: P. Wojciechowski, A. Lipowska, P. Rys, K. G. Ewens, S. Franks, S. Tan, E. Lerchbaum, J. Vcelak, R. Attaoua, M. Straczkowski, R. Azziz, T. M. Barber, A. Hinney, B. Obermayer-Pietsch, P. Lukasova, B. Bendlova, F. Grigorescu, I. Kowalska, M. O. Goodarzi, J. F. Strauss, M. I. McCarthy, M. T. Malecki
Institutions: Emory University, University of Pennsylvania, Hammersmith Hospital, Imperial College London, University of Duisburg-Essen, Medical University of Graz, Institute of Endocrinology, Institut Universitaire de Recherche Clinique, Nutrition et Alimentation des Populations aux Suds, Medical University of Białystok, University of Warwick, Cedars-Sinai Medical Center, Virginia Commonwealth University, Centre for Human Genetics, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Jagiellonian University, Szpital Uniwersytecki w Krakowie
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,490
Funders: Uniwersytet Jagielloński Collegium Medicum, Wellcome Trust, University of Exeter, Bundesministerium für Bildung und Forschung, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Verbundprojekt Molekulare Mechanismen der Adipositas - Identifizierung von Kandidatengenen, Statistik und Koordination (Teilprojekt 1, WB2-C, WB3-C, Teilprojekt15b, Teilprojekt16), Verbundvorhaben: Frühmanifeste Adipositas: Genetische Mechanismen und physiologische Implikationen, Teilprojekt 1, Translational Research in Polycystic Ovary Syndrome, Understanding the genetic basis of common human diseases: core funding for the Wellcome Trust Centre for Human Genetics., Diabetes Research Center (DRC)
OpenAlex ID: W2056017663