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http://dx.doi.org/10.4162/nrp.2012.6.1.78

Interactions between the $FTO$ rs9939609 polymorphism, body mass index, and lifestyle-related factors on metabolic syndrome risk  

Baik, In-Kyung (Department of Foods and Nutrition, College of Natural Sciences, Kookmin University)
Shin, Chol (Department of Internal Medicine, Korea University Ansan Hospital)
Publication Information
Nutrition Research and Practice / v.6, no.1, 2012 , pp. 78-85 More about this Journal
Abstract
Whether the $FTO$ polymorphisms interact with environmental factors has not yet been evaluated in associations with metabolic syndrome (MS) risk. The present study investigated the association of the $FTO$ rs9939609 genotypes, body mass index (BMI), and lifestyle-related factors including smoking, alcohol drinking, physical activity, and diet with MS incidence. A population-based prospective cohort study comprised 3,504 male and female Koreans aged 40 to 69 years. At the beginning of the study, all individuals were free of MS and known cardiovascular disease. Incident cases of MS were identified by biennial health examinations during a follow-up period from April 17, 2003 to April 15, 2009. Pooled logistic regression analysis was applied to obtain relative odds (RO) of MS with its 95% confidence interval (CI). After controlling for potential MS risk factors, we observed no association between the rs9939609 genotypes and MS incidence. In analysis stratified by BMI, however, carriers with the $FTO$ risk allele whose BMI is $29kg/m^2$ or greater showed an approximately 6-fold higher RO (95% CI: 3.82 to 9.30) compared with non-carriers with BMI less than $25kg/m^2$. In particular, the association between the rs9939609 variants and MS risk was significantly modified by high BMI (P-value for interaction < 0.05). Such significant interaction appeared in associations with central obesity and high blood pressure among the MS components. Because carriers of the $FTO$ risk alleles who had BMI of $29kg/m^2$ or greater are considered a high risk population, we suggest that they may need intensive weight loss regimens to prevent MS development.
Keywords
FTO polymorphism; metabolic syndrome incidence; body mass index; lifestyle; prospective study;
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1 Wahlen K, Sjolin E, Hoffstedt J. The common rs9939609 gene variant of the fat mass- and obesity-associated gene FTO is related to fat cell lipolysis. J Lipid Res 2008;49:607-11.   DOI
2 Tschritter O, Preissl H, Yokoyama Y, Machicao F, Haring HU, Fritsche A. Variation in the FTO gene locus is associated with cerebrocortical insulin resistance in humans. Diabetologia 2007; 50:2602-3.   DOI
3 Fischer J, Koch L, Emmerling C, Vierkotten J, Peters T, Brüning JC, Ruther U. Inactivation of the Fto gene protects from obesity. Nature 2009;458:894-8.   DOI
4 Zimmermann E, Kring SI, Berentzen TL, Holst C, Pers TH, Hansen T, Pedersen O, Sørensen TI, Jess T. Fatness-associated FTO gene variant increases mortality independent of fatness--in cohorts of Danish men. PLoS One 2009;4:e4428.   DOI
5 Li DP, Pan HL. Glutamatergic inputs in the hypothalamic paraventricular nucleus maintain sympathetic vasomotor tone in hypertension. Hypertension 2007;49:916-25.   DOI
6 Jonsson A, Renstrom F, Lyssenko V, Brito EC, Isomaa B, Berglund G, Nilsson PM, Groop L, Franks PW. Assessing the effect of interaction between an FTO variant (rs9939609) and physical activity on obesity in 15,925 Swedish and 2,511 Finnish adults. Diabetologia 2009;52:1334-8.   DOI
7 Lappalainen TJ, Tolppanen AM, Kolehmainen M, Schwab U, Lindström J, Tuomilehto J, Pulkkinen L, Eriksson JG, Laakso M, Gylling H, Uusitupa M; Finnish Diabetes Prevention Study Group. The common variant in the FTO gene did not modify the effect of lifestyle changes on body weight: the Finnish Diabetes Prevention Study. Obesity (Silver Spring) 2009;17:832-6.   DOI
8 Sonestedt E, Roos C, Gullberg B, Ericson U, Wirfält E, Orho- Melander M. Fat and carbohydrate intake modify the association between genetic variation in the FTO genotype and obesity. Am J Clin Nutr 2009;90:1418-25.   DOI
9 Andreasen CH, Stender-Petersen KL, Mogensen MS, Torekov SS, Wegner L, Andersen G, Nielsen AL, Albrechtsen A, Borch- Johnsen K, Rasmussen SS, Clausen JO, Sandbaek A, Lauritzen T, Hansen L, Jørgensen T, Pedersen O, Hansen T. Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation. Diabetes 2008;57:95-101.   DOI
10 Rampersaud E, Mitchell BD, Pollin TI, Fu M, Shen H, O'Connell JR, Ducharme JL, Hines S, Sack P, Naglieri R, Shuldiner AR, Snitker S. Physical activity and the association of common FTO gene variants with body mass index and obesity. Arch Intern Med 2008;168:1791-7.   DOI
11 Gonzalez-Sanchez JL, Zabena C, Martinez-Larrad MT, Martinez- Calatrava MJ, Perez-Barba M, Serrano-Rios M. Variant rs9939609 in the FTO gene is associated with obesity in an adult population from Spain. Clin Endocrinol (Oxf) 2009;70:390-3.   DOI
12 Xi B, Shen Y, Zhang M, Liu X, Zhao X, Wu L, Cheng H, Hou D, Lindpaintner K, Liu L, Mi J, Wang X. The common rs9939609 variant of the fat mass and obesity-associated gene is associated with obesity risk in children and adolescents of Beijing, China. BMC Med Genet 2010;11:107.
13 Cruz M, Valladares-Salgado A, Garcia-Mena J, Ross K, Edwards M, Angeles-Martinez J, Ortega-Camarillo C, de la Peña JE, Burguete-Garcia AI, Wacher-Rodarte N, Ambriz R, Rivera R, D'artote AL, Peralta J, Parra EJ, Kumate J. Candidate gene association study conditioning on individual ancestry in patients with type 2 diabetes and metabolic syndrome from Mexico City. Diabetes Metab Res Rev 2010;26:261-70.   DOI
14 Wang T, Huang Y, Xiao XH, Wang DM, Diao CM, Zhang F, Xu LL, Zhang YB, Li WH, Zhang LL, Zhang Y, Sun XF, Zhang Q. The association between common genetic variation in the FTO gene and metabolic syndrome in Han Chinese. Chin Med J (Engl) 2010;123:1852-8.
15 Baik I, Shin C. Prospective study of alcohol consumption and metabolic syndrome. Am J Clin Nutr 2008;87:1455-63.   DOI
16 Baik I, Cho NH, Kim SH, Han BG, Shin C. Genome-wide association studies identify genetic loci related to alcohol consumption in Korean men. Am J Clin Nutr 2011;93:809-16.   DOI
17 Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, Spertus JA, Costa F; American Heart Association; National Heart, Lung, and Blood Institute. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement. Circulation 2005;112:2735-52.   DOI
18 Baik I. Optimal cutoff points of waist circumference for the criteria of abdominal obesity: comparison with the criteria of the International Diabetes Federation. Circ J 2009;73:2068-75.   DOI
19 National Rural Living Science Institute. Food Composition Table, 5th ed. Suwon: Rural Development Administration; 1996.
20 Ahn Y, Kwon E, Shim JE, Park MK, Joo Y, Kimm K, Park C, Kim DH. Validation and reproducibility of food frequency questionnaire for Korean genome epidemiologic study. Eur J Clin Nutr 2007;61:1435-41.   DOI
21 Gerken T, Girard CA, Tung YC, Webby CJ, Saudek V, Hewitson KS, Yeo GS, McDonough MA, Cunliffe S, McNeill LA, Galvanovskis J, Rorsman P, Robins P, Prieur X, Coll AP, Ma M, Jovanovic Z, Farooqi IS, Sedgwick B, Barroso I, Lindahl T, Ponting CP, Ashcroft FM, O'Rahilly S, Schofield CJ. The obesityassociated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 2007;318:1469-72.   DOI
22 Church C, Moir L, McMurray F, Girard C, Banks GT, Teboul L, Wells S, Bruning JC, Nolan PM, Ashcroft FM, Cox RD. Overexpression of Fto leads to increased food intake and results in obesity. Nat Genet 2010;42:1086-92.   DOI
23 Tan JT, Dorajoo R, Seielstad M, Sim XL, Ong RT, Chia KS, Wong TY, Saw SM, Chew SK, Aung T, Tai ES. FTO variants are associated with obesity in the Chinese and Malay populations in Singapore. Diabetes 2008;57:2851-7.   DOI
24 Cho YS, Go MJ, Kim YJ, Heo JY, Oh JH, Ban HJ, Yoon D, Lee MH, Kim DJ, Park M, Cha SH, Kim JW, Han BG, Min H, Ahn Y, Park MS, Han HR, Jang HY, Cho EY, Lee JE, Cho NH, Shin C, Park T, Park JW, Lee JK, Cardon L, Clarke G, McCarthy MI, Lee JY, Lee JK, Oh B, Kim HL. A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits. Nat Genet 2009;41:527-34.   DOI
25 Nestel P, Lyu R, Low LP, Sheu WH, Nitiyanant W, Saito I, Tan CE. Metabolic syndrome: recent prevalence in East and Southeast Asian populations. Asia Pac J Clin Nutr 2007;16:362-7.
26 Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, Salonen JT. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002;288:2709-16.   DOI
27 Sjögren M, Lyssenko V, Jonsson A, Berglund G, Nilsson P, Groop L, Orho-Melander M. The search for putative unifying genetic factors for components of the metabolic syndrome. Diabetologia 2008;51:2242-51.   DOI
28 Legry V, Cottel D, Ferrieres J, Arveiler D, Andrieux N, Bingham A, Wagner A, Ruidavets JB, Ducimetiere P, Amouyel P, Meirhaeghe A. Effect of an FTO polymorphism on fat mass, obesity, and type 2 diabetes mellitus in the French MONICA Study. Metabolism 2009;58:971-5.   DOI
29 Pausova Z, Syme C, Abrahamowicz M, Xiao Y, Leonard GT, Perron M, Richer L, Veillette S, Smith GD, Seda O, Tremblay J, Hamet P, Gaudet D, Paus T. A common variant of the FTO gene is associated with not only increased adiposity but also elevated blood pressure in French Canadians. Circ Cardiovasc Genet 2009;2:260-9.   DOI
30 Al-Attar SA, Pollex RL, Ban MR, Young TK, Bjerregaard P, Anand SS, Yusuf S, Zinman B, Harris SB, Hanley AJ, Connelly PW, Huff MW, Hegele RA. Association between the FTO rs9939609 polymorphism and the metabolic syndrome in a non-Caucasian multi-ethnic sample. Cardiovasc Diabetol 2008;7:5.   DOI
31 Kring SI, Holst C, Zimmermann E, Jess T, Berentzen T, Toubro S, Hansen T, Astrup A, Pedersen O, Sørensen TI. FTO gene associated fatness in relation to body fat distribution and metabolic traits throughout a broad range of fatness. PLoS One 2008;3:e2958.   DOI
32 Freathy RM, Timpson NJ, Lawlor DA, Pouta A, Ben-Shlomo Y, Ruokonen A, Ebrahim S, Shields B, Zeggini E, Weedon MN, Lindgren CM, Lango H, Melzer D, Ferrucci L, Paolisso G, Neville MJ, Karpe F, Palmer CN, Morris AD, Elliott P, Jarvelin MR, Smith GD, McCarthy MI, Hattersley AT, Frayling TM. Common variation in the FTO gene alters diabetes-related metabolic traits to the extent expected given its effect on BMI. Diabetes 2008;57:1419-26.   DOI
33 Hubacek JA, Bohuslavova R, Kuthanova L, Kubinova R, Peasey A, Pikhart H, Marmot MG, Bobak M. The FTO gene and obesity in a large Eastern European population sample: the HAPIEE study. Obesity (Silver Spring) 2008;16:2764-6.   DOI
34 Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, Perry JR, Elliott KS, Lango H, Rayner NW, Shields B, Harries LW, Barrett JC, Ellard S, Groves CJ, Knight B, Patch AM, Ness AR, Ebrahim S, Lawlor DA, Ring SM, Ben-Shlomo Y, Jarvelin MR, Sovio U, Bennett AJ, Melzer D, Ferrucci L, Loos RJ, Barroso I, Wareham NJ, Karpe F, Owen KR, Cardon LR, Walker M, Hitman GA, Palmer CN, Doney AS, Morris AD, Smith GD, Hattersley AT, McCarthy MI. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 2007;316: 889-94.   DOI
35 Scuteri A, Sanna S, Chen WM, Uda M, Albai G, Strait J, Najjar S, Nagaraja R, Orrú M, Usala G, Dei M, Lai S, Maschio A, Busonero F, Mulas A, Ehret GB, Fink AA, Weder AB, Cooper RS, Galan P, Chakravarti A, Schlessinger D, Cao A, Lakatta E, Abecasis GR. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet 2007;3:e115.   DOI
36 Dina C, Meyre D, Gallina S, Durand E, Korner A, Jacobson P, Carlsson LM, Kiess W, Vatin V, Lecoeur C, Delplanque J, Vaillant E, Pattou F, Ruiz J, Weill J, Levy-Marchal C, Horber F, Potoczna N, Hercberg S, Le Stunff C, Bougnères P, Kovacs P, Marre M, Balkau B, Cauchi S, Chèvre JC, Froguel P. Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet 2007;39:724-6.   DOI
37 Hunt SC, Stone S, Xin Y, Scherer CA, Magness CL, Iadonato SP, Hopkins PN, Adams TD. Association of the FTO gene with BMI. Obesity (Silver Spring) 2008;16:902-4.   DOI
38 Song Y, You NC, Hsu YH, Howard BV, Langer RD, Manson JE, Nathan L, Niu T, Tinker LF, Liu S. FTO polymorphisms are associated with obesity but not diabetes risk in postmenopausal women. Obesity (Silver Spring) 2008;16:2472-80.   DOI
39 Horikoshi M, Hara K, Ito C, Shojima N, Nagai R, Ueki K, Froguel P, Kadowaki T. Variations in the HHEX gene are associated with increased risk of type 2 diabetes in the Japanese population. Diabetologia 2007;50:2461-6.   DOI
40 Li H, Wu Y, Loos RJ, Hu FB, Liu Y, Wang J, Yu Z, Lin X. Variants in the fat mass- and obesity-associated (FTO) gene are not associated with obesity in a Chinese Han population. Diabetes 2008;57:264-8.   DOI
41 Hotta K, Nakata Y, Matsuo T, Kamohara S, Kotani K, Komatsu R, Itoh N, Mineo I, Wada J, Masuzaki H, Yoneda M, Nakajima A, Miyazaki S, Tokunaga K, Kawamoto M, Funahashi T, Hamaguchi K, Yamada K, Hanafusa T, Oikawa S, Yoshimatsu H, Nakao K, Sakata T, Matsuzawa Y, Tanaka K, Kamatani N, Nakamura Y. Variations in the FTO gene are associated with severe obesity in the Japanese. J Hum Genet 2008;53:546-53.   DOI
42 Marvelle AF, Lange LA, Qin L, Adair LS, Mohlke KL. Association of FTO with obesity-related traits in the Cebu Longitudinal Health and Nutrition Survey (CLHNS) Cohort. Diabetes 2008;57: 1987-91.   DOI
43 Chang YC, Liu PH, Lee WJ, Chang TJ, Jiang YD, Li HY, Kuo SS, Lee KC, Chuang LM. Common variation in the fat mass and obesity-associated (FTO) gene confers risk of obesity and modulates BMI in the Chinese population. Diabetes 2008;57: 2245-52.   DOI