An FTO variant is associated with Type 2 diabetes in South Asian populations after accounting for body mass index and waist circumference
Rees, Simon D., Islam, M., Hydrie, M. Z. I., Chaudhary, B., Bellary, Srikanth, Hashmi, Shiraz, O’Hare, Joseph P., Kumar, Sudhesh, Sanghera, D. K., Chaturvedi, N., Barnett, A. H. (Anthony H.), 1951-, Shera, A. S., Weedon, Michael N., Basit, A. (Abdul), Frayling, Timothy M., Kelly, M. Ann and Jafar, T. H.. (2011) An FTO variant is associated with Type 2 diabetes in South Asian populations after accounting for body mass index and waist circumference. Diabetic Medicine, Volume 28 (Number 6). pp. 673-680. ISSN 0742-3071Full text not available from this repository.
Official URL: http://dx.doi.org/10.1111/j.1464-5491.2011.03257.x
A common variant, rs9939609, in the FTO (fat mass and obesity) gene is associated with adiposity in Europeans, explaining its relationship with diabetes. However, data are inconsistent in South Asians. Our aim was to investigate the association of the FTO rs9939609 variant with obesity, obesity-related traits and Type 2 diabetes in South Asian individuals, and to use meta-analyses to attempt to clarify to what extent BMI influences the association of FTO variants with diabetes in South Asians. Methods We analysed rs9939609 in two studies of Pakistani individuals: 1666 adults aged >= 40 years from the Karachi population-based Control of Blood Pressure and Risk Attenuation (COBRA) study and 2745 individuals of Punjabi ancestry who were part of a Type 2 diabetes case-control study (UK Asian Diabetes Study/Diabetes Genetics in Pakistan; UKADS/DGP). The main outcomes were BMI, waist circumference and diabetes. Regression analyses were performed to determine associations between FTO alleles and outcomes. Summary estimates were combined in a meta-analysis of 8091 South Asian individuals (3919 patients with Type 2 diabetes and 4172 control subjects), including those from two previous studies. Results In the 4411 Pakistani individuals from this study, the age-, sex- and diabetes-adjusted association of FTO variant rs9939609 with BMI was 0.45 (95% CI 0.24-0.67) kg/m2 per A-allele (P = 3.0 x 10-5) and with waist circumference was 0.88 (95% CI 0.36-1.41) cm per A-allele (P = 0.001). The A-allele (30% frequency) was also significantly associated with Type 2 diabetes [per A-allele odds ratio (95% CI) 1.18 (1.07-1.30); P = 0.0009]. A meta-analysis of four South Asian studies with 8091 subjects showed that the FTO A-allele predisposes to Type 2 diabetes [1.22 (95% CI 1.14-1.31); P = 1.07 x 10-8] even after adjusting for BMI [1.18 (95% CI 1.10-1.27); P = 1.02 x 10-5] or waist circumference [1.18 (95% CI 1.10-1.27); P = 3.97 x 10-5]. Conclusions The strong association between FTO genotype and BMI and waist circumference in South Asians is similar to that observed in Europeans. In contrast, the strong association of FTO genotype with diabetes is only partly accounted for by BMI.
|Item Type:||Journal Article|
|Subjects:||R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine
R Medicine > RC Internal medicine
|Divisions:||Faculty of Medicine > Warwick Medical School|
|Library of Congress Subject Headings (LCSH):||Non-insulin-dependent diabetes -- Risk factors, Non-insulin-dependent diabetes -- Genetic aspects, Non-insulin-dependent diabetes -- Susceptibility -- Research, South Asians -- Health and hygiene -- Research, Non-insulin-dependent diabetes -- South Asia, Body mass index, Obesity -- Genetic aspects|
|Journal or Publication Title:||Diabetic Medicine|
|Page Range:||pp. 673-680|
|Funder:||Wellcome Trust (London, England), Diabetes UK, Eli Lilly and Company, Pfizer Inc., Sanofi Aventis (Firm), Servier Laboratories UK, Merck Sharp & Dohme, Takeda UK (Firm), Roche, Daiichi-Sankyo UK, Boehringer Ingelheim Pharmaceuticals, Novo Nordisk, Bristol-Myers Squibb Company, Solvay Healthcare Ltd., Assurance Medical Society UK, Fogarty International Center, National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (NIDDKD)|
|Grant number:||080747/Z/06/Z (WT), 07/0003512, 09/0003926 (DUK), KO1 TW006087 (FIC), R01 DK082766 (NIDDKD)|
|References:||1 Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ. Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet 2006; 367: 1747–1757. 2 Jafar TH, Qadri Z, Chaturvedi N. Coronary artery disease epidemic in Pakistan: more electrocardiographic evidence of ischaemia in women than in men. Heart 2008; 94: 408–413. 3 Reddy KS. Cardiovascular disease in non-Western countries. N Engl J Med 2004; 350: 2438–2440. 4 Jafar TH, Levey AS, Jafary FH, White F, Gul A, Rahbar MH et al. Ethnic subgroup differences in hypertension in Pakistan. J Hypertens 2003; 21: 905–912. 5 Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 2007; 316: 889–894. 6 Andreasen CH, Stender-Petersen KL, Mogensen MS, Torekov SS, Wegner L, Andersen G et al. Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation. Diabetes 2008; 57: 95–101. 7 Renstrom F, Payne F, Nordstrom A, Brito EC, Rolandsson O, Hallmans G et al. Replication and extension of genome-wide association study results for obesity in 4923 adults from northern Sweden. Hum Mol Genet 2009; 18: 1489–1496. 8 Thorleifsson G, Walters GB, Gudbjartsson DF, Steinthorsdottir V, Sulem P, Helgadottir A et al. Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat Genet 2009; 41: 18–24. 9 Legry V, Cottel D, Ferrieres J, Arveiler D, Andrieux N, Bingham A et al. Effect of an FTO polymorphism on fat mass, obesity, and type 2 diabetes mellitus in the French MONICA Study. Metabolism 2009; 58: 971–975.10 Hertel JK, Johansson S, Raeder H, Midthjell K, Lyssenko V, Groop L et al. Genetic analysis of recently identified type 2 diabetes loci in 1638 unselected patients with type 2 diabetes and 1858 control participants from a Norwegian population-based cohort (the HUNT study). Diabetologia 2008; 51: 971–977. 11 Li H, Wu Y, Loos RJ, Hu FB, Liu Y, Wang J et al. Variants in the fat mass- and obesity-associated (FTO) gene are not associated with obesity in a Chinese Han population. Diabetes 2008; 57: 264– 268. 12 Tan JT, Dorajoo R, Seielstad M, Sim XL, Ong RT, Chia KS et al. FTO variants are associated with obesity in the Chinese and Malay populations in Singapore. Diabetes 2008; 57: 2851–2857. 13 Wu Y, Li H, Loos RJ, Yu Z, Ye X, Chen L et al. Common variants in CDKAL1, CDKN2A ⁄ B, IGF2BP2, SLC30A8, and HHEX ⁄ IDE genes are associated with type 2 diabetes and impaired fasting glucose in a Chinese Han population. Diabetes 2008; 57: 2834– 2842. 14 Hotta K, Nakata Y, Matsuo T, Kamohara S, Kotani K, Komatsu R et al. Variations in the FTO gene are associated with severe obesity in the Japanese. J Hum Genet 2008; 53: 546–553. 15 Tabara Y, Osawa H, Guo H, Kawamoto R, Onuma H, Shimizu I et al. Prognostic significance of FTO genotype in the development of obesity in Japanese: the J-SHIPP study. Int J Obes (Lond) 2009; 33: 1243–1248. 16 Yajnik CS, Janipalli CS, Bhaskar S, Kulkarni SR, Freathy RM, Prakash S et al. FTO gene variants are strongly associated with type 2 diabetes in South Asian Indians. Diabetologia 2009; 52: 247–252. 17 Sanghera DK, Ortega L, Han S, Singh J, Ralhan SK, Wander GS et al. Impact of nine common type 2 diabetes risk polymorphisms in Asian Indian Sikhs: PPARG2 (Pro12Ala), IGF2BP2, TCF7L2 and FTO variants confer a significant risk. BMC Med Genet 2008; 9: 59. 18 Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998; 15: 539–553. 19 Bellary S, O’Hare JP, Raymond NT, Gumber A, Mughal S, Szczepura A et al. Enhanced diabetes care to patients of south Asian ethnic origin (the UK Asian Diabetes Study): a cluster randomised controlled trial. Lancet 2008; 371: 1769–1776. 20 Misra A, Chowbey P, Makkar BM, Vikram NK, Wasir JS, Chadha D et al. Consensus statement for diagnosis of obesity, abdominal obesity and the metabolic syndrome for Asian Indians and recommendations for physical activity, medical and surgical management. J Assoc Physicians India 2009; 57: 163–170. 21 Bressler J, Kao WH, Pankow JS, Boerwinkle E. Risk of type 2 diabetes and obesity is differentially associated with variation in FTO in whites and African-Americans in the ARIC study. PLoS One 2010; 5: e10521. 22 Speliotes EK, Willer CJ, Berndt SI, Monda KL, Thorleifsson G, Jackson AU et al. Association analyses of 249 796 individuals reveal 18 new loci associated with body mass index. Nat Genet 2010; 42: 937–948. 23 Dhawan J, Bray CL, Warburton R, Ghambhir DS, Morris J. Insulin resistance, high prevalence of diabetes, and cardiovascular risk in immigrant Asians. Genetic or environmental effect? Br Heart J 1994; 72: 413–421. 24 Jafar TH, Chaturvedi N, Pappas G. Prevalence of overweight and obesity and their association with hypertension and diabetes mellitus in an Indo-Asian population. CMAJ 2006; 175: 1071–1077.|
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