The Library

An FTO variant is associated with Type 2 diabetes in South Asian populations after accounting for body mass index and waist circumference

Tools

Rees, Simon D., Islam, M., Hydrie, M. Z. I., Chaudhary, B., Bellary, Srikanth, Hashmi, Shiraz, O'Hare, J. Paul, Kumar, Sudhesh, Sanghera, D. K., Chaturvedi, N., Barnett, A. H., Shera, A. S., Weedon, Michael N., Basit, A., 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 0742-3071

Full text not available from this repository.

Official URL: http://dx.doi.org/10.1111/j.1464-5491.2011.03257.x

Abstract

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

Publisher:

Blackwell

ISSN:

0742-3071

Official Date:

2011

Dates:

Date	Event
2011	Published

Volume:

Volume 28

Number:

Number 6

Page Range:

pp. 673-680

Identification Number:

10.1111/j.1464-5491.2011.03257.x

Status:

Peer Reviewed

Publication Status:

Published

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.