Obesity is associated with a variety of adverse health risks. Several genome-wide association studies of obesity have identified candidate genes, including the fat mass and obesity-associated gene (FTO) and the melanocortin-4 receptor (MC4R) gene. We carried out a replication study of MC4R and FTO variants in a Korean cohort. A total of 2,281 subjects in the Bundang-gu region were analyzed using selected markers. Another 8,826 subjects in the Ansung/Ansan city were used for a meta-analysis. Two single nucleotide polymorphisms (SNPs) in FTO and one SNP in the MC4R gene were genotyped. Multivariate linear regression models were employed to test for genotypic effects on obesity traits while adjusting for age and sex using an additive model. The SNP rs17782313 near the MC4R gene was associated with mean body mass index in the Bundang-gu cohort (effect per allele 0.288 kg/m2, p = 0.0023). The p value for meta-analysis of rs17782313 in all 11,107 individuals in the Bundang-gu and Ansung/Ansan cohorts was 2.82 × 10−6 (effect per allele 0.22 kg/m2). Two SNPs in FTO were significantly associated with weight (effect per allele 0.969 kg, p = 0.011 for rs9939609; 0.943, p = 0.014 for rs8050136) but not with body mass index. This study demonstrates that genetic variants in MC4R influence obesity traits in Korean adults.
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S. Klein, L.E. Burke, G.A. Bray, S. Blair, D.B. Allison, X. Pi-Sunyer et al., Clinical implications of obesity with specific focus on cardiovascular disease: a statement for professionals from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism: endorsed by the American College of Cardiology Foundation. Circulation 110, 2952–2967 (2004)
T. Rankinen, A. Zuberi, Y.C. Chagnon, S.J. Weisnagel, G. Argyropoulos, B. Walts, L. Pérusse, C. Bouchard, The human obesity gene map: the 2005 update. Obesity(Silver Spring) 14, 529–644 (2006)
T.M. Frayling, N.J. Timpson, M.N. Weedon, E. Zeggini, R.M. Freathy, C.M. Lindgren et al., A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316, 889–894 (2007)
A. Scuteri, S. Sanna, W.M. Chen, M. Uda, G. Albai, J. Strait, S. Najjar, R. Nagaraja, M. Orrú, G. Usala, M. Dei, S. Lai, A. Maschio, F. Busonero, A. Mulas, G.B. Ehret, A.A. Fink, A.B. Weder, R.S. Cooper, P. Galan, A. Chakravarti, D. Schlessinger, A. Cao, E. Lakatta, G.R. Abecasis, Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet. 3, e115 (2007)
R.J. Loos, C.M. Lindgren, S. Li, E. Wheeler, J.H. Zhao, I. Prokopenko et al., Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat. Genet. 40, 768–775 (2008)
C.J. Willer, E.K. Speliotes, R.J. Loos, S. Li, C.M. Lindgren, I.M. Heid et al., Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat. Genet. 41, 25–34 (2009)
D. Meyre, J. Delplanque, J.C. Chèvre, C. Lecoeur, S. Lobbens, S. Gallina et al., Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations. Nat. Genet. 41, 157–159 (2009)
D.P. Zobel, C.H. Andreasen, N. Grarup, H. Eiberg, T.I. Sørensen, A. Sandbaek, T. Lauritzen, K. Borch-Johnsen, T. Jørgensen, O. Pedersen, T. Hansen, Variants near MC4R are associated with obesity and influence obesity-related quantitative traits in a population of middle-aged people: studies of 14,940 Danes. Diabetes 58, 757–764 (2009)
S. Beckers, D. Zegers, F. de Freitas, I.L. Mertens, L.F. Van Gaal, W. Van Hul, Association study of MC4R with complex obesity and replication of the rs17782313 association signal. Mol. Genet. Metab. 103, 71–75 (2011)
J. Shi, J. Long, Y.T. Gao, W. Lu, Q. Cai, W. Wen, Y. Zheng, K. Yu, Y.B. Xiang, F.B. Hu, W. Zheng, X.O. Shu, Evaluation of genetic susceptibility loci for obesity in Chinese women. Am. J. Epidemiol. 172, 244–254 (2010)
K. Hotta, M. Nakamura, T. Nakamura, T. Matsuo, Y. Nakata, S. Kamohara et al., Association between obesity and polymorphisms in SEC16B, TMEM18, GNPDA2, BDNF, FAIM2 and MC4R in a Japanese population. J. Hum. Genet. 54, 727–731 (2009)
C.Y. Cheung, A.W. Tso, B.M. Cheung, A. Xu, K.L. Ong, C.H. Fong, N.M. Wat, E.D. Janus, P.C. Sham, K.S. Lam, Obesity susceptibility genetic variants identified from recent genome-wide association studies: implications in a chinese population. J. Clin. Endocrinol. Metab. 95, 1395–1403 (2010)
W. Huang, Y. Sun, J. Sun, Combined effects of FTO rs9939609 and MC4R rs17782313 on obesity and BMI in Chinese Han populations. Endocrine 39, 69–74 (2011)
S. Cauchi, F. Stutzmann, C. Cavalcanti-Proença, E. Durand, A. Pouta, A.L. Hartikainen et al., Combined effects of MC4R and FTO common genetic variants on obesity in European general populations. J. Mol. Med. 87, 537–546 (2009)
F. Renström, F. Payne, A. Nordström, E.C. Brito, O. Rolandsson, G. Hallmans et al., Replication and extension of genome-wide association study results for obesity in 4923 adults from northern Sweden. Hum. Mol. Genet. 18, 1489–1496 (2009)
Y.S. Cho, M.J. Go, Y.J. Kim, J.Y. Heo, J.H. Oh, H.J. Ban, D. Yoon, M.H. Lee, D.J. Kim, M. Park, S.H. Cha, J.W. Kim, B.G. Han, H. Min, Y. Ahn, M.S. Park, H.R. Han, H.Y. Jang, E.Y. Cho, J.E. Lee, N.H. Cho, C. Shin, T. Park, J.W. Park, J.K. Lee, L. Cardon, G. Clarke, M.I. McCarthy, J.Y. Lee, J.K. Lee, B. Oh, H.L. Kim, A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits. Nat. Genet. 41, 527–534 (2009)
Y. Okada, M. Kubo, H. Ohmiya, A. Takahashi, N. Kumasaka, N. Hosono, S. Maeda, W. Wen, R. Dorajoo, M.J. Go, W. Zheng, N. Kato, J.Y. Wu, Q. Lu, GIANT consortium, T. Tsunoda, K. Yamamoto, Y. Nakamura, N. Kamatani, T. Tanaka, Common variants at CDKAL1 and KLF9 are associated with body mass index in East Asian populations. Nat. Genet. 44, 302–306 (2012)
L. Hui, T. DelMonte, K. Ranade, Genotyping using the TaqMan assay. Curr. Protoc. Hum. Genet. (2008). doi:10.1002/0471142905.hg0210s56. Chapter 2, Unit 2.10
J.P. Ioannidis, N.A. Patsopoulos, E. Evangelou, Heterogeneity in meta-analyses of genome-wide association investigations. PLoS ONE 2, e841 (2007)
G. Lurie, M.M. Gaudet, A.B. Spurdle, M.E. Carney, L.R. Wilkens, H.P. Yang et al., The obesity-associated polymorphisms FTO rs9939609 and MC4R rs17782313 and endometrial cancer risk in non-Hispanic white women. PLoS ONE 6, e16756 (2011)
L. Qi, P. Kraft, D.J. Hunter, F.B. Hu, The common obesity variant near MC4R gene is associated with higher intakes of total energy and dietary fat, weight change and diabetes risk in women. Hum. Mol. Genet. 17, 3502–3508 (2008)
F. Stutzmann, S. Cauchi, E. Durand, C. Calvacanti-Proença, M. Pigeyre, A.L. Hartikainen, U. Sovio, J. Tichet, M. Marre, J. Weill, B. Balkau, N. Potoczna, J. Laitinen, P. Elliott, M.R. Järvelin, F. Horber, D. Meyre, P. Froguel, Common genetic variation near MC4R is associated with eating behaviour patterns in European populations. Int. J. Obes. (Lond) 33, 373–378 (2009)
S.I. Kring, C. Holst, S. Toubro, A. Astrup, T. Hansen, O. Pedersen, T.I. Sørensen et al., Common variants near MC4R in relation to body fat, body fat distribution, metabolic traits and energy expenditure. Int. J. Obes. (Lond) 34, 182–189 (2010)
M.C. Ng, K.S. Park, B. Oh, C.H. Tam, Y.M. Cho, H.D. Shin, V.K. Lam, R.C. Ma, W.Y. So, Y.S. Cho, H.L. Kim, H.K. Lee, J.C. Chan, N.H. Cho, Implication of genetic variants near TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, and FTO in type 2 diabetes and obesity in 6,719 Asians. Diabetes 57, 2226–2233 (2008)
Y.C. Chang, P.H. Liu, W.J. Lee, T.J. Chang, Y.D. Jiang, H.Y. Li, S.S. Kuo, K.C. Lee, L.M. Chuang, Common variation in the fat mass and obesity-associated (FTO) gene confers risk of obesity and modulates BMI in the Chinese population. Diabetes 57, 2245–2252 (2008)
J.T. Tan, R. Dorajoo, M. Seielstad, X.L. Sim, R.T. Ong, K.S. Chia, T.Y. Wong, S.M. Saw, S.K. Chew, T. Aung, E.S. Tai, FTO variants are associated with obesity in the Chinese and Malay populations in Singapore. Diabetes 57, 2851–2857 (2008)
F. Takeuchi, K. Yamamoto, T. Katsuya, T. Nabika, T. Sugiyama, A. Fujioka, M. Isono, K. Ohnaka, T. Fujisawa, E. Nakashima, H. Ikegami, J. Nakamura, Y. Yamori, S. Yamaguchi, S. Kobayashi, T. Ogihara, R. Takayanagi, N. Kato, Association of genetic variants for susceptibility to obesity with type 2 diabetes in Japanese individuals. Diabetologia (2011). doi:10.1007/s00125-011-2086-8
E. Rampersaud, B.D. Mitchell, T.I. Pollin, M. Fu, H. Shen, J.R. O’Connell, J.L. Ducharme, S. Hines, P. Sack, R. Naglieri, A.R. Shuldiner, S. Snitker, Physical activity and the association of common FTO gene variants with body mass index and obesity. Arch. Intern. Med. 168, 1791–1797 (2008)
E. Sonestedt, C. Roos, B. Gullberg, U. Ericson, E. Wirfält, M. Orho-Melander, Fat and carbohydrate intake modify the association between genetic variation in the FTO genotype and obesity. Am. J. Clin. Nutr. 90, 1418–1425 (2009)
This research was supported by Eulji University in 2011 and by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (2012010044).
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The authors declare no conflict of interest.
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Sull, J.W., Lee, M. & Jee, S.H. Replication of genetic effects of MC4R polymorphisms on body mass index in a Korean population. Endocrine 44, 675–679 (2013). https://doi.org/10.1007/s12020-013-9909-y
- Body mass index