Lifestyle genomics and the metabolic syndrome: A review of genetic variants that influence response to diet and exercise interventions

References

• Austin, M. A., M. C. King, R. D. Bawol, S. B. Hulley, and G. D. Friedman. 1987. Risk factors for coronary heart disease in adult female twins. Genetic heritability and shared environmental influences. American Journal of Epidemiology 125 (2):308–18.
   PubMed Web of Science ®Google Scholar
• Bassi, N., I. Karagodin, S. Wang, P. Vassallo, A. Priyanath, E. Massaro, and N. J. Stone. 2014. Lifestyle modification for metabolic syndrome: A systematic review. American Journal of Medicine 127 (12):1242.e1–10. doi:10.1016/j.amjmed.2014.06.035.
   Web of Science ®Google Scholar
• Blanchard, B. E., G. J. Tsongalis, M. A. Guidry, L. A. LaBelle, M. Poulin, A. L. Taylor, C. M. Maresh, J. Devaney, P. D. Thompson, and L. S. Pescatello. 2006. RAAS polymorphisms alter the acute blood pressure response to aerobic exercise among men with hypertension. European Journal of Applied Physiology 97 (1):26–33. doi:10.1007/s00421-006-0142-8.
   PubMed Web of Science ®Google Scholar
• Bouchard, C., S. N. Blair, T. S. Church, C. P. Earnest, J. M. Hagberg, K. Hakkinen, N. T. Jenkins, L. Karavirta, W. E. Kraus, A. S. Leon, et al. 2012. Adverse Metabolic response to regular exercise: Is it a rare or common occurrence? Plos One 7 (5):e37887. doi:10.1371/journal.pone.0037887.
   PubMed Web of Science ®Google Scholar
• Bouchard, C., A. Tremblay, J. P. Després, A. Nadeau, P. J. Lupien, G. Thériault, J. Dussault, S. Moorjani, S. Pinault, and G. Fournier. 1990. The response to long-term overfeeding in identical twins. New England Journal of Medicine 322 (21):1477–82. doi:10.1056/NEJM199005243222101.
   PubMed Web of Science ®Google Scholar
• Brown, A. E., and M. Walker. 2016. Genetics of insulin resistance and the metabolic syndrome. Current Cardiology Reports 18 (8):75. doi:10.1007/s11886-016-0755-4.
   PubMed Web of Science ®Google Scholar
• Carvalho, S. S., A. C. Simões e Silva, A. Sabino, F. C. G. Evangelista, K. B. Gomes, L. M. SantAna Dusse, and D. R. Alves Rios. 2016. Influence of ACE I/D polymorphism on circulating levels of plasminogen activator inhibitor 1, D-Dimer, Ultrasensitive C-Reactive protein and transforming growth factor β1 in patients undergoing hemodialysis. Plos One 11 (3):e0150613. doi:10.1371/journal.pone.0150613.
   PubMed Web of Science ®Google Scholar
• Corbalán, M. S., A. Marti, L. Forga, M. A. Martínez-Gonzalez, and J. A. Martínez. 2002. The risk of obesity and the Trp64Arg polymorphism of the β(3)-adrenergic receptor: Effect modification by age. Annals of Nutrition & Metabolism 46 (3–4):152–58. doi:10.1159/000063084.
   PubMed Web of Science ®Google Scholar
• Corella, D., P. Carrasco, J. V. Sorlí, R. Estruch, J. Rico-Sanz, M. Á. Martínez-González, J. Salas-Salvadó, M. I. Covas, O. Coltell, F. Arós, et al. 2013. Mediterranean diet reduces the adverse effect of the TCF7L2-rs7903146 polymorphism on cardiovascular risk factors and stroke incidence: A randomized controlled trial in a high-cardiovascular-risk population. Diabetes Care 36 (11):3803–11. doi:10.2337/dc13-0955.
   PubMed Web of Science ®Google Scholar
• Cui, G., Z. Li, R. Li, J. Huang, H. Wang, L. Zhang, H. Ding, and D. Wen Wang. 2014. A functional variant in APOA5/A4/C3/A1 gene cluster contributes to elevated triglycerides and severity of CAD by interfering with MicroRNA 3201 binding efficiency. Journal of the American College of Cardiology 64 (3):267–77. doi:10.1016/j.jacc.2014.03.050.
   PubMed Web of Science ®Google Scholar
• Deeb, S. S., L. Fajas, M. Nemoto, J. Pihlajamäki, L. Mykkänen, J. Kuusisto, M. Laakso, W. Fujimoto, and J. Auwerx. 1998. A Pro12Ala substitution in PPARgamma2 Associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nature Genetics 20 (3):284–87. doi:10.1038/3099.
   PubMed Web of Science ®Google Scholar
• Delahanty, L. M., Q. Pan, K. A. Jablonski, K. E. Watson, M. Jeanne, A. Shuldiner, S. E. Kahn, W. C. Knowler, J. C. Florez, and P. W. Franks. 2012. Genetic predictors of weight loss and weight regain after intensive lifestyle modification, metformin treatment, or standard care in the Diabetes prevention program. Diabetes Care 35:363–66. doi:10.2337/dc11-1328.
   PubMed Web of Science ®Google Scholar
• Dongen, J., G. Willemsen, W. M. Chen, E. J. de Geus, and D. I. Boomsma. 2013. Heritability of metabolic syndrome traits in a large population-based sample. Journal of Lipid Research 54 (10):2914–23. doi:10.1194/jlr.P041673.
   PubMed Web of Science ®Google Scholar
• Drenjančević-Perić, I., B. Jelaković, J. H. Lombard, M. P. Kunert, A. Kibel, and M. Gros. 2011. High-salt diet and hypertension: Focus on the renin-angiotensin system. Kidney & Blood Pressure Research 34 (1):1–11. doi:10.1159/000320387.
   PubMed Web of Science ®Google Scholar
• Dupuis, J., C. Langenberg, I. Prokopenko, R. Saxena, N. Soranzo, A. U. Jackson, E. Wheeler, N. L. Glazer, N. Bouatia-Naji, A. L. Gloyn, et al. 2010. New genetic Loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nature Genetics 42 (2):105–16. doi:10.1038/ng.520.
   PubMed Web of Science ®Google Scholar
• Ehret, G. B., T. Ferreira, D. I. Chasman, A. U. Jackson, E. M. Schmidt, T. Johnson, G. Thorleifsson, J. Luan, L. A. Donnelly, S. Kanoni, et al. 2016. The genetics of blood pressure regulation and its target organs from association studies in 342,415 Individuals. Nature Genetics 48 (10):1171–84. doi:10.1038/ng.3667.
   PubMed Web of Science ®Google Scholar
• Eichner, J. E., S. T. Dunn, G. Perveen, D. M. Thompson, K. E. Stewart, and B. C. Stroehla. 2002. Apolipoprotein E polymorphism and cardiovascular disease: a HuGE Review. American Journal of Epidemiology 155 (6):487–95. http://www.ncbi.nlm.nih.gov/pubmed/11882522.
   PubMed Web of Science ®Google Scholar
• Felder, R. A., M. J. White, S. M. Williams, and P. A. Jose. 2013. Diagnostic tools for hypertension and salt sensitivity testing. Current Opinion in Nephrology and Hypertension 22 (1):65–76. doi:10.1097/MNH.0b013e32835b3693.
   PubMed Web of Science ®Google Scholar
• Florez, J. C., K. A. Jablonski, N. Bayley, T. I. Pollin, P. I. W. de Bakker, A. R. Shuldiner, W. C. Knowler, D. M. Nathan, D. Altshuler, and Diabetes Prevention Program Research Group. 2006. TCF7L2 polymorphisms and progression to diabetes in the diabetes prevention program. New England Journal of Medicine 355 (3):241–50. doi:10.1056/NEJMoa062418.
   PubMed Web of Science ®Google Scholar
• Frayling, T. M., N. J. Timpson, M. N. Weedon, E. Zeggini, R. M. Freathy, C. M. Lindgren, J. R. B Perry, K. S. Elliott, H. Lango, N. W. Rayner, et al. 2007. A Common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 11 (316):889–94. doi:10.1126/science.1141634.
   Google Scholar
• Garaulet, M., C. E. Smith, T. Hernandez-Gonzalez, Y. Lee, and J.M. Ordovas. 2011. PPARγ Pro12Ala interacts with fat intake for obesity and weight loss in a behavioural treatment based on the mediterranean diet. Molecular Nutrition & Food Research 55 (12):1771–79. doi:10.1002/mnfr.201100437.PPAR.
   PubMed Web of Science ®Google Scholar
• Garcia, M., J. Bihuniak, J. Shook, A. Kenny, J. Kerstetter, and T. Huedo-Medina. 2016. The effect of the traditional mediterranean-style diet on metabolic risk factors: A meta-analysis. Nutrients 8 (3):168. doi:10.3390/nu8030168.
   PubMed Web of Science ®Google Scholar
• Ge, D., H. Zhu, Y. Huang, F. A. Treiber, G. A. Harshfield, H. Snieder, and Y. Dong. 2007. Multilocus analyses of renin-angiotensin-aldosterone system gene variants on blood pressure at rest and during behavioral stress in young normotensive subjects. Hypertension 49 (1):107–12. doi:10.1161/01.HYP.0000251524.00326.e7.
   PubMed Web of Science ®Google Scholar
• Giner, V., E. Poch, E. Bragulat, J. Oriola, D. González, A. Coca, and A. De La Sierra. 2000. Renin-angiotensin system genetic polymorphisms and salt sensitivity in essential hypertension. Hypertension 35 (1 Pt 2):512–17. http://www.ncbi.nlm.nih.gov/pubmed/10642351.
   PubMed Web of Science ®Google Scholar
• Goessler, K. F., V. A. Cornelissen, E. M. de Oliveira, G. de F Mota, and M. D Polito. 2015. ACE polymorphisms and the acute response of blood pressure to a walk in medicated hypertensive patients. Journal of the Renin-Angiotensin-Aldosterone System 16 (4):720–29. doi:10.1177/1470320315600086.
   PubMed Web of Science ®Google Scholar
• Goyenechea, E., M. D. Parra, and J. A. Martínez. 2006. Weight regain after slimming induced by an energy-restricted diet depends on Interleukin-6 and Peroxisome-proliferator-activated-receptor-gamma2 gene polymorphisms. British Journal of Nutrition 96 (5):965–72. doi:10.1017/BJN20061901.
   PubMed Web of Science ®Google Scholar
• Grygiel-Górniak, B. 2014. Peroxisome proliferator-activated receptors and their ligands: Nutritional and clinical implications – a review. Nutrition Journal 13 (1):17. doi:10.1186/1475-2891-13-17.
   PubMedGoogle Scholar
• Guardiola, M., and J. Ribalta. 2017. Update on APOA5 genetics: Toward a better understanding of its physiological impact. Current Atherosclerosis Reports 19 (7):30. doi:10.1007/s11883-017-0665-y.
   PubMed Web of Science ®Google Scholar
• Guionnet, M. G. 2008. Role of the APOA5 gene in lipid and fat-soluble vitamin metabolism. Universitat Rovira I Virgili. http://www.tesisenred.net/bitstream/handle/10803/8857/tesimontse.pdf?sequence = 1&isAllowed = y.
   Google Scholar
• Hansen, P. A., D. H. Han, B. A. Marshall, L. A. Nolte, M. M. Chen, M. Mueckler, and J. O. Holloszy. 1998. A high fat diet impairs stimulation of glucose transport in muscle. Functional evaluation of potential mechanisms. Journal of Biological Chemistry 273 (40):26157–63.
   PubMed Web of Science ®Google Scholar
• Haupt, A., C. Thamer, M. Heni, O. Tschritter, J. Machann, F. Schick, F. Machicao, H. U. Häring, H. Staiger, and A. Fritsche. 2009. Impact of variation near mc4r on whole-body fat distribution, liver fat, and weight loss. Obesity (Silver Spring) 17 (10):1942–45. doi:10.1038/oby.2009.233.
   PubMed Web of Science ®Google Scholar
• Heller, D. A., U. de Faire, N. L. Pedersen, G. Dahlen, and G. E. McClearn. 1993. Genetic and environmental influences on serum lipid levels in twins. New England Journal of Medicine 328 (16):1150–56. doi:10.1056/NEJM199304223281603.
   PubMed Web of Science ®Google Scholar
• Hinney, A., C. I. G. Vogel, and J. Hebebrand. 2010. From monogenic to polygenic obesity: Recent advances. European Child & Adolescent Psychiatry 19 (3):297–310. doi:10.1007/s00787-010-0096-6.
   PubMed Web of Science ®Google Scholar
• Hiraga, H., T. Oshima, M. Watanabe, M. Ishida, T. Ishida, T. Shingu, M. Kambe, H. Matsuura, and G. Kajiyama. 1996. Angiotensin I–converting enzyme gene polymorphism and salt sensitivity in essential hypertension. Hypertension 27 (3):569–72. https://www.ncbi.nlm.nih.gov/pubmed/8613205.
   PubMed Web of Science ®Google Scholar
• Huang, T., Q. Qi, Y. Li, F. B. Hu, G. A. Bray, F. M. Sacks, D. A. Williamson, and L. Qi. 2014. FTO genotype, dietary protein, and change in appetite: The preventing overweight using novel dietary strategies trial. American Journal of Clinical Nutrition 99 (5):1126–30. doi:10.3945/ajcn.113.082164.
   PubMed Web of Science ®Google Scholar
• Huang, T., S. H. Ley, Y. Zheng, T. Wang, G. A. Bray, F. M. Sacks, and L. Qi. 2016. Genetic susceptibility to diabetes and long-term improvement of insulin resistance and β cell function during weight loss: The preventing overweight using novel dietary strategies (POUNDS LOST) Trial. American Journal of Clinical Nutrition 104 (1):198–204. doi:10.3945/ajcn.115.121186.
   PubMed Web of Science ®Google Scholar
• Huggins, G. S., G. D. Papandonatos, B. Erar, L. M. Belalcazar, A. Brautbar, C. Ballantyne, A. E. Kitabchi, L. E. Wagenknecht, W. C. Knowler, H. J. Pownall, et al. 2013. Do genetic modifiers of high-density lipoprotein cholesterol and triglyceride levels also modify their response to a lifestyle intervention in the setting of obesity and type-2 diabetes mellitus? The action for health in diabetes (Look AHEAD) Study. Circulation Cardiovascular Genetics 6 (4):391–99. doi:10.1161/CIRCGENETICS.113.000042.
   PubMed Web of Science ®Google Scholar
• IDF Worldwide Definition of the Metabolic Syndrome | International Diabetes Federation. 2005. http://www.idf.org/metabolic-syndrome.
   Google Scholar
• Jang, Y., J. S. Chae, O. Y. Kim, H. J. Park, J. Y. Kim, J. K. Paik, S. H. Lee, and J. H. Lee. 2010. APOA5-1131T>C genotype effects on apolipoprotein A5 and triglyceride levels in response to dietary intervention and regular exercise (DIRE) in hypertriglyceridemic subjects. Atherosclerosis 211 (2):512–19. doi:10.1016/j.atherosclerosis.2010.03.014.
   PubMed Web of Science ®Google Scholar
• Jin, T. 2016. Current understanding on role of the Wnt signaling pathway effector TCF7L2 in glucose homeostasis. Endocrine Reviews 37 (3):254–77. doi:10.1210/er.2015-1146.
   PubMed Web of Science ®Google Scholar
• Jones, A., H. E. Montgomery, and D. R. Woods. 2002. Human performance: A role for the ACE genotype? Exercise and Sport Sciences Reviews 30 (4):184–90. http://www.ncbi.nlm.nih.gov/pubmed/12398116.
   PubMed Web of Science ®Google Scholar
• Kaur, J. 2014. A comprehensive review on metabolic syndrome. Cardiology Research and Practice 2014:943162. doi:10.1155/2014/943162.
   PubMedGoogle Scholar
• Kelly, T., W. Yang, C.-S. Chen, K. Reynolds, and J. He. 2008. Global burden of obesity in 2005 and projections to 2030. International Journal of Obesity 32 (9):1431–37. doi:10.1038/ijo.2008.102.
   PubMed Web of Science ®Google Scholar
• Khan, R. J., S. Y. Gebreab, M. Sims, P. Riestra, R. Xu, and S. K. Davis. 2015. Prevalence, associated factors and heritabilities of metabolic syndrome and its individual components in African Americans: The Jackson heart study. BMJ Open 5 (10):e008675. doi:10.1136/bmjopen-2015-008675.
   PubMed Web of Science ®Google Scholar
• Kim, K. 2009. Association of angiotensin-converting enzyme insertion/deletion polymorphism with obesity, cardiovascular risk factors and exercise-mediated changes in Korean women. European Journal of Applied Physiology 105 (6):879–87. doi:10.1007/s00421-008-0973-6.
   PubMed Web of Science ®Google Scholar
• Knowler, W. C., E. Barrett-Connor, S. E. Fowler, R. F. Hamman, J. M. Lachin, E. A. Walker, D. M. Nathan, and Diabetes Prevention Program Research Group. 2002. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. New England Journal of Medicine 346 (6):393–403. doi:10.1056/NEJMoa012512.
   PubMed Web of Science ®Google Scholar
• Kovacs, P., R. L. Hanson, Y.-H. Lee, X. Yang, S. Kobes, P. A. Permana, C. Bogardus, and L. J. Baier. 2003. The role of insulin receptor substrate-1 Gene (IRS1) in type 2 diabetes in Pima Indians. Diabetes 52 (12):3005–9. https://www.ncbi.nlm.nih.gov/pubmed/14633864.
   PubMed Web of Science ®Google Scholar
• Kristiansson, K., M. Perola, E. Tikkanen, J. Kettunen, I. Surakka, A. S. Havulinna, A. Stančáková, C. Barnes, E. Widen, E. Kajantie, et al. 2012. Genome-wide screen for metabolic syndrome susceptibility Loci reveals strong lipid gene contribution but no evidence for common genetic basis for clustering of metabolic syndrome traits. Circulation Cardiovascular Genetics 5 (2):242–49. doi:10.1161/CIRCGENETICS.111.961482.
   PubMed Web of Science ®Google Scholar
• Kullo, I. J., H. Jouni, E. E. Austin, S.-A. Brown, T. M. Kruisselbrink, I. N. Isseh, R. A. Haddad, T. S. Marroush, K. Shameer, J. E. Olson, et al. 2016. Incorporating a genetic risk score into coronary heart disease risk estimates: Effect on low-density lipoprotein cholesterol levels (the MI-GENES Clinical Trial). Circulation 133 (12):1181–88. doi:10.1161/CIRCULATIONAHA.115.020109.
   PubMed Web of Science ®Google Scholar
• Kuriyama, S., T. Shimazu, A. Hozawa, S. Kure, N. Kurokawa, M. Kakizaki, T. Sone, K. Matsuda-Ohmori, N. Nakaya, H. Satoh, et al. 2008. No effect of the Trp64Arg variant of the β3-adrenergic receptor gene on weight loss by diet and exercise intervention among Japanese Adults. Metabolism 57 (11):1570–75. doi:10.1016/j.metabol.2008.06.013.
   PubMed Web of Science ®Google Scholar
• Kurokawa, N. 2011. Association of BMI with the beta3 adrenergic receptor gene mutation: A meta-analysis. Japanese Journal of Hygiene 66 (1):42–46. doi:10.1265/jjh.66.42.
   PubMedGoogle Scholar
• Kurokawa, N., E. H. Young, Y. Oka, H. Satoh, N. J. Wareham, M. S. Sandhu, and R. J. F. Loos. 2008. The ADRB3 Trp64Arg variant and BMI: A meta-analysis of 44 833 individuals. International Journal of Obesity 32 (8):1240–49. doi:10.1038/ijo.2008.90.
   Web of Science ®Google Scholar
• Laukkanen, O., J. Pihlajamäki, J. Lindström, J. Eriksson, T. T. Valle, H. Hämäläinen, P. Ilanne-Parikka, S. Keinänen-Kiukaanniemi, J. Tuomilehto, M. Uusitupa, et al. 2004. Common polymorphisms in the genes regulating the early insulin signalling pathway: Effects on weight change and the conversion from impaired glucose tolerance to Type 2 diabetes. The finnish diabetes prevention study. Diabetologia. 47 (5):871–77. doi:10.1007/s00125-004-1395-6.
   PubMed Web of Science ®Google Scholar
• Leiter, L. A., D. H. Fitchett, R. E. Gilbert, M. Gupta, G. B. Mancini, P. A. McFarlane, R. Ross, H. Teoh, S. Verma, S. Anand, et al. 2011. Cardiometabolic risk in canada: A detailed analysis and position paper by the cardiometabolic risk working group. Canadian Journal of Cardiology 27 (2):e1–33. doi:10.1016/j.cjca.2010.12.054.
   PubMed Web of Science ®Google Scholar
• Lindi, V. I., M. I. J. Uusitupa, J. Lindström, A. Louheranta, J. G. Eriksson, T. T. Valle, H. Hämäläinen, P. Ilanne-Parikka, S. Keinänen-Kiukaanniemi, M. Laakso, et al. 2002. Association of the Pro12Ala Polymorphism in the PPAR-γ2 gene with 3-year incidence of type 2 diabetes and body weight change in the finnish diabetes prevention study. Diabetes 51 (8):2581–86. doi:10.2337/diabetes.51.8.2581.
   PubMed Web of Science ®Google Scholar
• Lindström, J., A. Louheranta, M. Mannelin, M. Rastas, V. Salminen, J. Eriksson, M. Uusitupa, and J. Tuomilehto. 2003. The finnish diabetes prevention study (DPS). Diabetes Care 26 (12). doi:10.2337/diacare.26.12.3230.
   Web of Science ®Google Scholar
• Livingstone, K. M., C. Celis-Morales, G. D. Papandonatos, B. Erar, J. C. Florez, K. A. Jablonski, C. Razquin, A. Marti, Y. Heianza, T. Huang, et al. 2016. FTO genotype and weight loss: Systematic review and meta-analysis of 9563 individual participant data from eight randomised controlled trials. BMJ 354:i4707. doi:10.1136/bmj.i4707.
   PubMedGoogle Scholar
• Loos, R. J. F., C. M. Lindgren, S. Li, E. Wheeler, J. H. Zhao, I. Prokopenko, M. Inouye, R. M Freathy, A. P. Attwood, J. S. Beckmann, et al. 2008. Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nature Genetics 40 (6):768–75. doi:10.1038/ng.140.
   PubMed Web of Science ®Google Scholar
• Lyssenko, V., R. Lupi, P. Marchetti, S. Del Guerra, M. Orho-Melander, P. Almgren, M. Sjögren, C. Ling, K. F. Eriksson, A. L. Lethagen, et al. 2007. Mechanisms by which common variants in the TCF7L2 gene increase risk of Type 2 Diabetes. Journal of Clinical Investigation 117 (8):2155–63. doi:10.1172/JCI30706.
   PubMed Web of Science ®Google Scholar
• Martínez, J. A., and F. I. Milagro. 2015. Genetics of weight loss: A basis for personalized obesity management. Trends in Food Science & Technology 42 (2):97–115. doi:10.1016/j.tifs.2014.12.007.
   Web of Science ®Google Scholar
• Matsuo, T., Y. Nakata, Y. Katayama, M. Iemitsu, S. Maeda, T. Okura, M.-K. Kim, H. Ohkubo, K. Hotta, and K. Tanaka. 2009. PPARG genotype accounts for part of individual variation in body weight reduction in response to calorie restriction. Obesity (Silver Spring) 17 (10):1924–31. doi:10.1038/oby.2009.199.
   PubMed Web of Science ®Google Scholar
• Melanson, E. L., S. K. Keadle, J. E. Donnelly, B. Braun, and N. A. King. 2013. Resistance to exercise-induced weight loss: Compensatory behavioral adaptations. Medicine and Science in Sports and Exercise 45 (8):1600–09. doi:10.1249/MSS.0b013e31828ba942.
   PubMed Web of Science ®Google Scholar
• Mohlke, K. L., and M. Boehnke. 2015. Recent advances in understanding the genetic architecture of type 2 diabetes. Human Molecular Genetics 24 (R1):R85–92. doi:10.1093/hmg/ddv264.
   PubMed Web of Science ®Google Scholar
• Moore, A. F., K. A. Jablonski, C. C. Mason, J. B. McAteer, R. F. Arakaki, B. J. Goldstein, S. E. Kahn, A. E. Kitabchi, R. L. Hanson, W. C. Knowler, et al. 2009. The association of ENPP1 K121Q with diabetes incidence is abolished by lifestyle modification in the diabetes prevention program. Journal of Clinical Endocrinology and Metabolism 94 (2):449–55. doi:10.1210/jc.2008-1583.
   PubMed Web of Science ®Google Scholar
• Mota, R. M., R. J. Oliveira, D. F. Terra, E. Pardono, M. T. Dutra, J. A. de Almeida, and F. M. Silva. 2013. Acute and chronic effects of resistance exercise on blood pressure in elderly women and the possible influence of ACE I/D polymorphism. International Journal of General Medicine 6:581–87. doi:10.2147/IJGM.S40628.
   PubMedGoogle Scholar
• Mulè, G., I. Calcaterra, E. Nardi, G. Cerasola, and S. Cottone. 2014. Metabolic syndrome in hypertensive patients: An unholy alliance. World Journal of Cardiology 6 (9):890–907. doi:10.4330/wjc.v6.i9.890.
   PubMedGoogle Scholar
• Mutch, D. M., and K. Clément. 2006. Unraveling the genetics of human obesity. PLoS Genetics 2 (12):e188. doi:10.1371/journal.pgen.0020188.
   PubMed Web of Science ®Google Scholar
• Norris, J. M., and S. S. Rich. 2012. Genetics of glucose homeostasis: Implications for insulin resistance and metabolic syndrome. Arteriosclerosis, Thrombosis, and Vascular Biology 32 (9):2091–96. doi:10.1161/ATVBAHA.112.255463.
   PubMed Web of Science ®Google Scholar
• Pan, Q., L. M. Delahanty, K. A. Jablonski, W. C. Knowler, S. E. Kahn, J. C. Florez, and P. W. Franks. 2013. Variation at the melanocortin 4 receptor gene and response to weight-loss interventions in the diabetes prevention program. Obesity 21 (9):520–26. doi:10.1002/oby.20459.
   Web of Science ®Google Scholar
• Perez-Martinez, P., A. I. Perez-Caballero, A. Garcia-Rios, E. M. Yubero-Serrano, A. Camargo, M. J. Gomez-Luna, C. Marin, P. Gomez-Luna, A. Dembinska-Kiec, F. Rodriguez-Cantalejo, et al. 2012. Effects of rs7903146 Variation in the Tcf7l2 gene in the lipid metabolism of three different populations. Plos One 7 (8):e43390. doi:10.1371/journal.pone.0043390.
   PubMed Web of Science ®Google Scholar
• Plum, L. A., and H. F. DeLuca. 2010. Vitamin D, disease and therapeutic opportunities. Nature Reviews Drug Discovery 9 (12):941–55. doi:10.1038/nrd3318.
   PubMed Web of Science ®Google Scholar
• Poch, E., D. González, V. Giner, E. Bragulat, A. Coca, and A. de la Sierra. 2001. Molecular basis of salt sensitivity in human hypertension. Hypertension 38 (5):1204–9.
   PubMed Web of Science ®Google Scholar
• Povel, C. M., J. M. A. Boer, E. Reiling, and E. J. M. Feskens. 2011. Genetic variants and the metabolic syndrome: A systematic review. Obesity Reviews 12 (11):952–67. doi:10.1111/j.1467-789X.2011.00907.x.
   PubMed Web of Science ®Google Scholar
• Qi, Q., G. A. Bray, S. R. Smith, F. B. Hu, F. M. Sacks, and L. Qi. 2011. Insulin receptor substrate 1 gene variation modifies insulin resistance response to weight-loss diets in a 2-year randomized trial: The preventing overweight using novel dietary strategies (POUNDS LOST) Trial. Circulation 124 (5):563–71. doi:10.1161/CIRCULATIONAHA.111.025767.
   PubMed Web of Science ®Google Scholar
• Razquin, C., J. A. Martinez, M. A. Martinez-Gonzalez, M. Bes-Rastrollo, J. Fernández-Crehuet, and A. Marti. 2010. A 3-year intervention with a mediterranean diet modified the association between the rs9939609 gene variant in FTO and body weight changes. International Journal of Obesity 34 (2):266–72. doi:10.1038/ijo.2009.233.
   PubMed Web of Science ®Google Scholar
• Reinehr, T., J. Hebebrand, S. Friedel, A. M. Toschke, H. Brumm, H. Biebermann, and A. Hinney. 2009. Lifestyle intervention in obese children with variations in the melanocortin 4 receptor gene. Obesity (Silver Spring) 17 (2):382–89. doi:10.1038/oby.2008.422.
   PubMed Web of Science ®Google Scholar
• Roberts, C. K., A. L. Hevener, and R. J. Barnard. 2013. Metabolic syndrome and insulin resistance: Underlying causes and modification by exercise training. Comprehensive Physiology 3 (1):1–58. doi:10.1002/cphy.c110062.
   PubMed Web of Science ®Google Scholar
• Roche, H. M., C. Phillips, and M. J. Gibney. 2005. The metabolic syndrome: The crossroads of diet and genetics. The Proceedings of the Nutrition Society 64 (3):371–77. http://www.ncbi.nlm.nih.gov/pubmed/16048671.
   PubMed Web of Science ®Google Scholar
• Rönn, T., P. Volkov, C. Davegårdh, T. Dayeh, E. Hall, A. H. Olsson, E. Nilsson, A. Tornberg, M. Dekker Nitert, K. F. Eriksson, et al. 2013. A six months exercise intervention influences the genome-wide DNA methylation pattern in human adipose tissue. PLoS Genetics 9 (6):e1003572. doi:10.1371/journal.pgen.1003572.
   PubMed Web of Science ®Google Scholar
• Rung, J., S. Cauchi, A. Albrechtsen, L. Shen, G. Rocheleau, C. Cavalcanti-Proença, F. Bacot, B. Balkau, A. Belisle, K. Borch-Johnsen, et al. 2009. Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia. Nature Genetics 41 (10):1110–15. doi:10.1038/ng.443.
   PubMed Web of Science ®Google Scholar
• Sacks, F. M., G. A. Bray, V. J. Carey, S. R. Smith, D. H. Ryan, S. D. Anton, K. McManus, C. M. Champagne, L. M. Bishop, N. Laranjo, et al. 2009. Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. New England Journal of Medicine 360 (9):859–73. doi:10.1056/NEJMoa0804748.
   PubMed Web of Science ®Google Scholar
• Sakane, N., J. Sato, K. Tsushita, S. Tsujii, K. Kotani, M. Tominaga, and S. Kawazu. 2016. Effects of lifestyle intervention on weight and metabolic parameters in patients with impaired glucose tolerance related to Beta-3 adrenergic receptor gene polymorphism Trp64Arg (C/T): Results from the Japan diabetes prevention program. Journal of Diabetes Investigation 7 (3):338–42. doi:10.1111/jdi.12426.
   PubMed Web of Science ®Google Scholar
• Saliba, L. F., R. S. Reis, R. C. Brownson, A. A. Hino, L. V. Tureck, C. Valko, R. L. R. de Souza, and L. Furtado-Alle. 2014. Obesity-related gene ADRB2, ADRB3 and GHRL polymorphisms and the response to a weight loss diet intervention in adult women. Genetics and Molecular Biology 37 (1):15–22. doi:10.1590/S1415-47572014000100005.
   PubMed Web of Science ®Google Scholar
• Scuteri, A., S. Sanna, W. M. Chen, M. Uda, G. Albai, J. Strait, S. Najjar, R. Nagaraja, M. Orrú, G. Usala, et al. 2007. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genetics 3 (7):1200–10. doi:10.1371/journal.pgen.0030115.
   Web of Science ®Google Scholar
• Sharma, A. M., and B. Staels. 2007. Review: peroxisome proliferator-activated receptor gamma and adipose tissue–understanding obesity-related changes in regulation of lipid and glucose metabolism. Journal of Clinical Endocrinology and Metabolism 92 (2):386–95. doi:10.1210/jc.2006-1268.
   PubMed Web of Science ®Google Scholar
• Shih, P. B., and D. T. O'Connor. 2008. Hereditary determinants of human hypertension: Strategies in the setting of genetic complexity. Hypertension 51 (6):1456–64. doi:10.1161/HYPERTENSIONAHA.107.090480.
   PubMed Web of Science ®Google Scholar
• Shulman, G. I., S. Camilleri, S. M. Furler, D. J. Chisholm, and E. W. Kraegen. 2000. Cellular mechanisms of insulin resistance. Journal of Clinical Investigation 106 (2):171–76. doi:10.1172/JCI10583.
   PubMed Web of Science ®Google Scholar
• Siitonen, N., J. Lindström, J. Eriksson, T. T. Valle, H. Hämäläinen, P. Ilanne-Parikka, S. Keinänen-Kiukaanniemi, J. Tuomilehto, M. Laakso, and M. Uusitupa. 2004. Association between a deletion/insertion polymorphism in the alpha2B-adrenergic receptor gene and insulin secretion and Type 2 Diabetes. The Finnish diabetes prevention study. Diabetologia 47 (8):1416–24. doi:10.1007/s00125-004-1462-z.
   PubMed Web of Science ®Google Scholar
• Speakman, J. R. 2015. The ‘Fat mass and obesity related’ (FTO) Gene: Mechanisms of impact on obesity and energy balance. Current Obesity Reports 4 (1):73–91. doi:10.1007/s13679-015-0143-1.
   PubMed Web of Science ®Google Scholar
• Stankakova A., and M. Laakso. 2014. Genetics of metabolic syndrome. Reviews in Endocrine & Metabolic Disorders 15 (4):243–52. doi:10.1007/s11154-014-9293-9.
   PubMed Web of Science ®Google Scholar
• Tahara, A., Y. Osaki, and T. Kishimoto. 2010. Effect of the β3-adrenergic receptor gene polymorphism Trp64Arg on BMI reduction associated with an exercise-based intervention program in japanese middle-aged males. Environmental Health and Preventive Medicine 15 (6):392–97. doi:10.1007/s12199-010-0157-y.
   PubMedGoogle Scholar
• Tao, Y.-X. 2010. The melanocortin-4 receptor: physiology, pharmacology, and pathophysiology. Endocrine Reviews 31 (4):506–43. doi:10.1210/er.2009-0037.
   PubMed Web of Science ®Google Scholar
• Tchernof, A., R. D. Starling, A. Turner, A. R. Shuldiner, J. D. Walston, K. Silver, and E. T. Poehlman. 2000. Impaired capacity to lose visceral adipose tissue during weight reduction in obese postmenopausal women with the Trp64Arg beta3-adrenoceptor gene variant. Diabetes 49:1709–13. https://www.ncbi.nlm.nih.gov/pubmed/11016455.
   PubMed Web of Science ®Google Scholar
• Teslovich, T. M., K. Musunuru, A. V. Smith, A. C. Edmondson, I. M. Stylianou, M. Koseki, J. P. Pirruccello, S. Ripatti, D. I. Chasman, C. J. Willer, et al. 2010. Biological, clinical and population relevance of 95 Loci for Blood Lipids. Nature 466 (7307):707–13. doi:10.1038/nature09270.
   PubMed Web of Science ®Google Scholar
• Todorova, B., A. Kubaszek, J. Pihlajamäki, J. Lindström, J. Eriksson, T. T. Valle, H. Hämäläinen, P. Ilanne-Parikka, S. Keinänen-Kiukaanniemi, J. Tuomilehto, et al. 2004. The G-250A promoter polymorphism of the hepatic lipase gene predicts the conversion from impaired glucose tolerance to Type 2 diabetes mellitus: The finnish diabetes prevention study. Journal of Clinical Endocrinology and Metabolism 89 (5):2019–23. doi:10.1210/jc.2003-031325.
   PubMed Web of Science ®Google Scholar
• Tucker, A. J., K. A. Mackay, L. E. Robinson, T. E. Graham, M. Bakovic, and A. M. Duncan. 2010. The effect of whole grain wheat sourdough bread consumption on serum lipids in healthy normoglycemic/normoinsulinemic and hyperglycemic/hyperinsulinemic adults depends on presence of the APOE E3/E3 Genotype: A randomized controlled trial. Nutrition and Metabolism 7:37. doi:10.1186/1743-7075-7-37.
   Google Scholar
• Tung, Y. C, S. H. Giles, S. O'Rahilly, and A. P. Coll. 2014. Obesity and FTO: Changing focus at a complex locus. Cell Metabolism 20 (5):710–18. doi:10.1016/j.cmet.2014.09.010.
   PubMed Web of Science ®Google Scholar
• Vogels, N., E. C. Mariman, F. G. Bouwman, A. D. Kester, K. Diepvens, and M. S. Westerterp-Plantenga. 2005. Relation of weight maintenance and dietary restraint to peroxisome proliferator-activated receptor γ2, glucocorticoid receptor, and ciliary neurotrophic factor polymorphisms. American Journal of Clinical Nutrition 82 (4):740–46.
   PubMed Web of Science ®Google Scholar
• Wang, H., S. Dong, H. Xu, J. Qian, and J. Yang. 2012. Genetic variants in FTO associated with metabolic syndrome: A meta- and gene-based analysis. Molecular Biology Reports 39 (5):5691–98. doi:10.1007/s11033-011-1377-y.
   PubMed Web of Science ®Google Scholar
• White, U. A., and Y. D. Tchoukalova. 2014. Sex dimorphism and depot differences in adipose tissue function. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1842 (3):377–92. doi:10.1016/j.bbadis.2013.05.006.
   PubMed Web of Science ®Google Scholar
• Woehning, A., J.-H. Schultz, E. Roeder, A. Moeltner, B. Isermann, P. P. Nawroth, C. Wolfrum, and G. Rudofsky. 2012. The A-Allele of the common FTO gene variant rs9939609 complicates weight maintenance in severe obese patients. International Journal of Obesity 37 (1):135–39. doi:10.1038/ijo.2012.14.
   Web of Science ®Google Scholar
• Zhang, X., Q. Qi, G. A. Bray, F. B. Hu, F. M. Sacks, and L. Qi. 2012. APOA5 genotype modulates 2-Y changes in lipid profile in response to weight-loss diet intervention: The pounds lost trial. American Journal of Clinical Nutrition 96 (4):917–22. doi:10.3945/ajcn.112.040907.
   PubMed Web of Science ®Google Scholar
• Zlatohlavek, L., M. Vrablik, R. Ceska, V. Adamkova, Z. Urbanova, M. Prusikova, L. Vasickova, and J.A. Hubacek. 2012. APOA5 haplotypes determine triglyceride decrease after lifestyle induced weight loss in children. Nutrition, Metabolism and Cardiovascular Diseases 22 (9):e22–3. doi:10.1016/j.numecd.2012.05.001.
   PubMed Web of Science ®Google Scholar