ADRB2, ADRB3, BDKRB2 and MTNR1B Genes Related to Body fat Modulation and Its Interaction with Physical Activity and Blood Pressure
Author(s)
Aline Marcadenti1,2
Affiliation(s)
1 Department of Nutrition, Universidade Federal de Ciências da Saúde de Porto Alegre (UFSCPA), Porto Alegre, Brazil. 2 Postgraduate Studies Program in Cardiology, Instituto de Cardiologia/Funda??o Universitária de Cardiologia do Rio Grande do Sul (IC/FUC), Porto Alegre, Brazil .
1 Department of Nutrition, Universidade Federal de Ciências da Saúde de Porto Alegre (UFSCPA), Porto Alegre, Brazil. 2 Postgraduate Studies Program in Cardiology, Instituto de Cardiologia/Funda??o Universitária de Cardiologia do Rio Grande do Sul (IC/FUC), Porto Alegre, Brazil .
ABSTRACT
Hypertension (HTN) is the risk factor that most contributes to mortality rates in the world, followed by physical inactivity and obesity. Despite the influence of genetic factors on the genesis of HTN, blood pressure levels are strongly influenced by environmental factors such as physical inactivity and overweight, characterizing it as a polygenic disease. Genetic components and environmental factors such as physical exercise may modulate the phenotype of individuals predisposed to medical conditions such as HTN, independently of modifiable factors such as increased levels of adiposity; however, studies have shown that polymorphic forms detected in genes involved in the mechanisms of blood pressure regulation and also related to body fat modulation may interact with physical activity levels and HTN. The aim of this article is to review the interactions between polymorphisms in ADRB2, ADRB3, BDKRB2 and MTNR1B genes, physical activity and blood pressure.
Hypertension (HTN) is the risk factor that most contributes to mortality rates in the world, followed by physical inactivity and obesity. Despite the influence of genetic factors on the genesis of HTN, blood pressure levels are strongly influenced by environmental factors such as physical inactivity and overweight, characterizing it as a polygenic disease. Genetic components and environmental factors such as physical exercise may modulate the phenotype of individuals predisposed to medical conditions such as HTN, independently of modifiable factors such as increased levels of adiposity; however, studies have shown that polymorphic forms detected in genes involved in the mechanisms of blood pressure regulation and also related to body fat modulation may interact with physical activity levels and HTN. The aim of this article is to review the interactions between polymorphisms in ADRB2, ADRB3, BDKRB2 and MTNR1B genes, physical activity and blood pressure.
Cite this paper
Marcadenti, A. (2015) ADRB2, ADRB3, BDKRB2 and MTNR1B Genes Related to Body fat Modulation and Its Interaction with Physical Activity and Blood Pressure. Open Journal of Endocrine and Metabolic Diseases, 5, 88-97. doi: 10.4236/ojemd.2015.57012.
Marcadenti, A. (2015) ADRB2, ADRB3, BDKRB2 and MTNR1B Genes Related to Body fat Modulation and Its Interaction with Physical Activity and Blood Pressure. Open Journal of Endocrine and Metabolic Diseases, 5, 88-97. doi: 10.4236/ojemd.2015.57012.
References
[1] World Health Organization (WHO) (2009) Global Health Risks: Mortality and Burden of Disease Attributable to Selected Major Risks. WHO Press, Geneva. [2] Global Burden of Metabolic Risk Factors for Chronic Diseases Collaboration (2014) Cardiovascular Disease, Chronic Kidney Disease, and Diabetes Mortality Burden of Cardiometabolic Risk Factors from 1980 to 2010: A Comparative Risk Assessment. The Lancet Diabetes & Endocrinology, 2, 634-647.
http://dx.doi.org/10.1016/S2213-8587(14)70102-0 [3] Kearney, P.M., Whelton, M., Reynolds, K,, Muntner, P., Whelton, P.K. and He, J. (2005) Global Burden of Hypertension: Analysis of Worldwide Data. The Lancet, 365, 217-223. http://dx.doi.org/10.1016/S0140-6736(05)70151-3 [4] Brasil. Ministério da Saúde. Secretaria de Vigilancia em Saúde. (2014) Vigitel Brazil 2013: Protective and Risk Factors for Chronic Diseases by Telephone Survey. Ministério da Saúde, Secretaria de Vigilancia em Saúde. Ministério da Saúde, Brasília. [5] Lee, I.M., Shiroma, E.J., Lobelo, F., Puska, P., Blair, S.N. and Katzmarzyk, P.T., Lancet Physical Activity Series Working Group (2012) Effect of Physical Inactivity on Major Non-Communicable Diseases Worldwide: An Analysis of Burden of Disease and Life Expectancy. The Lancet, 380, 219-229.
http://dx.doi.org/10.1016/S0140-6736(12)61031-9 [6] Pischon, T., Boeing, H., Hoffmann, K., Bergmann, M., Schulze, M.B., Overvad, K., et al. (2008) General and Abdominal Adiposity and Risk of Death in Europe. New England Journal of Medicine, 359, 2105-2120. http://dx.doi.org/10.1056/NEJMoa0801891 [7] Kelly, T., Yang, W., Chen, C.S., Reynolds, K. and He, J. (2008) Global Burden of Obesity in 2005 and Projections to 2030. International Journal of Obesity (Lond), 32, 1431-1437.
http://dx.doi.org/10.1038/ijo.2008.102 [8] Beevers, G., Lip, G.Y.H. and O’Brien, E. (2001) ABC of Hypertension: The Pathophysiology of Hypertension. BMJ, 322, 912-916. http://dx.doi.org/10.1136/bmj.322.7291.912 [9] Sanjuliani, A.F. (2002) Pathophysiology of Hypertension: Useful Theoretical Concepts for Clinical Practice. Revista SOCERJ, 15, 210-218. [10] Carvalho, J.J., Baruzzi, R.G., Howard, P.F., Poulter, N., Alpers, M.P., Franco, L.J., et al. (1989) Blood Pressure in Four Remote Populations in the INTERSALT Study. Hypertension, 14, 238-246.
http://dx.doi.org/10.1161/01.HYP.14.3.238 [11] Schlaich, M.P., Klingbeil, A.U., Jacobi, J., Delles, C., Schneider, M.P., Schmidt, B.M., et al. (2002) Altered Aldosterone Response to Salt Intake and Angiotensin II Infusion in Young Normotensive Men with Parental History of Arterial Hypertension. Journal of Hypertension, 20, 117-124.
http://dx.doi.org/10.1097/00004872-200201000-00017 [12] Campos, L.A., Cipolla-Neto, J., Amaral, F.G., Michelini, L.C., Bader, M. and Baltatu, O.C. (2013) The Angiotensin-Melatonin Axis. International Journal of Hypertension, 2013, Article ID: 521783. [13] Francischetti, E.A. and Genelhu, V.A. (2007) Obesity-Hypertension: An Ongoing Pandemic. International Journal of Clinical Practice, 61, 269-280. http://dx.doi.org/10.1111/j.1742-1241.2006.01262.x [14] Nielsen, S., Guo, Z., Johnson, C.M., Hensrud, D.D. and Jensen, M.D. (2004) Splanchnic Lipolysis in Human Obesity. Journal of Clinical Investigation, 113, 1582-1588. http://dx.doi.org/10.1172/JCI21047 [15] Hall, J.E., da Silva, A.A., do Carmo, J.M., Dubinion, J., Hamza, S., Munusamy, S., et al. (2010) Obesity-Induced Hypertension: Role of Sympathetic Nervous System, Leptin, and Melanocortins. Journal of Biological Chemistry, 285, 17271-17276. http://dx.doi.org/10.1074/jbc.R110.113175 [16] Miall, W.E. and Oldham, P.D. (1963) The Hereditary Factor in Arterial Blood-Pressure. BMJ, 1, 75-80. http://dx.doi.org/10.1136/bmj.1.5323.75 [17] Ehret, G.B. and Caulfield, M.J. (2013) Genes for Blood Pressure: An Opportunity to Understand Hypertension. European Heart Journal, 34, 951-961. http://dx.doi.org/10.1093/eurheartj/ehs455 [18] Bauman, A.E., Reis, R.S., Sallis, J.F., Wells, J.C., Loos, R.J. and Martin, B.W., Lancet Physical Activity Series Working Group (2012) Correlates of Physical Activity: Why Are Some People Physically Active and Others Not? Lancet, 380, 258-271. http://dx.doi.org/10.1016/S0140-6736(12)60735-1 [19] Klingberg, F. and Klengel, S. (1993) Lesions in Four Parts of the Basal Forebrain Change Basic Behavior in Rats. NeuroReport, 4, 639-642. http://dx.doi.org/10.1097/00001756-199306000-00009 [20] Simonen, R.L., Perusse, L., Rankinen, T., Rice, T., Rao, D.C. and Bouchard, C. (2002) Familial Aggregation of Physical Activity Levels in the Quebec Family Study. Medicine & Science in Sports & Exercise, 34, 1137-1142. http://dx.doi.org/10.1097/00005768-200207000-00014 [21] Aaltonen, S., Ortega-Alonso, A., Kujala, U.M. and Kaprio, J. (2010) A Longitudinal Study on Genetic and Environmental Influences on Leisure Time Physical Activity in the Finnish Twin Cohort. Twin Research and Human Genetics, 13, 475-481. http://dx.doi.org/10.1375/twin.13.5.475 [22] Ekelund, U., Brage, S., Besson, H., Sharp, S. and Wareham, N.J. (2008) Time Spent Being Sedentary and Weight Gain in Healthy Adults: Reverse or Bidirectional Causality? American Journal of Clinical Nutrition, 88, 612-617. [23] Metcalf, B.S., Hosking, J., Jeffery, A.N., Voss, L.D., Henley, W. and Wilkin, T.J. (2011) Fatness Leads to Inactivity, but Inactivity Does Not Lead to Fatness: A Longitudinal Study in Children. Archives of Disease in Childhood, 96, 942-947. http://dx.doi.org/10.1136/adc.2009.175927 [24] Allison, D.B., Faith, M.S. and Nathan, J.S. (1996) Risch’s Lambda Values for Human Obesity. International Journal of Obesity and Related Metabolic Disorders, 20, 990-999. [25] Bouchard, C. (2008) Gene-Environment Interactions in the Etiology of Obesity: Defining the Fundamentals. Obesity, 16, S5-S10. http://dx.doi.org/10.1038/oby.2008.528 [26] Manolio, T.A. (2010) Genomewide Association Studies and Assessment of the Risk of Disease. New England Journal of Medicine, 363, 166-176. http://dx.doi.org/10.1056/NEJMra0905980 [27] Chorostowska-Wynimko, J. (2002) Mechanism of B2-Agonists Action and Safety Aspects. Polski Merkuriusz Lekarski, 12, 441-444. [28] Snyder, E.M., Johnson, B.D. and Joyner, M.J. (2008) Genetics of β2-Adrenergic Receptors and the Cardiopulmonary Response to Exercise. Exercise and Sport Sciences Reviews, 2, 98-105.
http://dx.doi.org/10.1097/JES.0b013e318168f276 [29] Balligand, J.L. (2013) β3-Adrenoreceptors in Cardiovascular Diseases: New Roles for an “Old” Receptor. Current Drug Delivery, 10, 64-66. http://dx.doi.org/10.2174/1567201811310010011 [30] Zhang, H., Wu, J. and Yu, L. (2014) Association of Gln27Glu and Arg16Gly Polymorphisms in β2-Adrenergic Receptor Gene with Obesity Susceptibility: A Meta-Analysis. PLoS ONE, 9, e100489.
http://dx.doi.org/10.1371/journal.pone.0100489 [31] Snyder, E.M., Beck, K.C., Dietz, N.M., Eisenach, J.H., Joyner, M.J., Turner, S.T., et al. (2006) Arg16Gly Polymorphism of the β2-Adrenergic Receptor is Associated with Differences in Cardiovascular Function at Rest and during Exercise in Humans. The Journal of Physiology, 571, 121-30.
http://dx.doi.org/10.1113/jphysiol.2005.098558 [32] Sipil?inen, R., Uusitupa, M., Heikkinen, S., Rissanen, A. and Laakso, M. (1997) Polymorphism of the β3-Adrenergic Receptor Gene Affects Basal Metabolic Rate in Obese Finns. Diabetes, 46, 77-80.
http://dx.doi.org/10.2337/diabetes.46.1.77 [33] Villares, S.M., Mancini, M.C., Gomez, S., Charf, A.M., Frazzatto, E. and Halpern, A. (2000) Association between Polymorphism Gln27Glu of β2-Adrenergic Receptor and Hypertension in Morbid Obese. Arquivos Brasileiros de Endo crinologia e Metabologia, 44, 72-80. [34] Rauhio, A., Uusi-Rasi, K., Nikkari, S.T., Kannus, P., Siev?nen, H. and Kunnas, T. (2013) Association of the FTO and ADRB2 Genes with Body Composition and Fat Distribution in Obese Women. Maturitas, 76, 165-171. http://dx.doi.org/10.1016/j.maturitas.2013.07.004 [35] Macho-Azcarate, T., Marti, A., González, A., Martinez, J.A. and Iba?ez, J. (2002) Gln27Glu Polymorphism in the beta2 Adrenergic Receptor Gene and Lipid Metabolism during Exercise in Obese Women. International Journal of Obesity and Related Metabolic Disorders, 26, 1434-1441.
http://dx.doi.org/10.1038/sj.ijo.0802129 [36] Lagou, V., Liu, G., Zhu, H., Stallmann-Jorgensen, I.S., Gutin, B., Dong, Y., et al. (2011) Lifestyle and Socioeconomic-Status Modify the Effects of ADRB2 and NOS3 on Adiposity in European-American and African-American Adolescents. Obesity, 19, 595-603. http://dx.doi.org/10.1038/oby.2010.224 [37] Ochoa, M.C., Moreno-Aliaga, M.J., Martínez-González, M.A., Martínez, J.A. and Marti, A., GENOI Members (2006) TV Watching Modifies Obesity Risk Linked to the 27Glu Polymorphism of the ADRB2 Gene in Girls. International Journal of Pediatric Obesity, 1, 83-88. http://dx.doi.org/10.1080/17477160600650386 [38] Nakashima, H., Omae, K., Nomiyama, T., Yamano, Y., Takebayashi, T. and Sakurai, Y. (2013) Beta-3-Adrenergic Receptor Trp64Arg Polymorphism: Does It Modulate the Relationship between Exercise and Percentage of Body Fat in Young Adult Japanese Males? Environmental Health and Preventive Medicine, 18, 323-329. http://dx.doi.org/10.1007/s12199-012-0325-3 [39] Saliba, L.F., Reis, R.S., Brownson, R.C., Hino, A.A., Tureck, L.V., Valko, C., et al. (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, 15-22.
http://dx.doi.org/10.1590/S1415-47572014000100005 [40] Brondani, L.A., Duarte, G.C., Canani, L.H. and Crispim, D. (2014) The Presence of at Least Three Alleles of the ADRB3 Trp64Arg (C/T) and UCP1-3826A/G Polymorphisms Is Associated with Protection to Overweight/Obesity and with Higher High-Density Lipoprotein Cholesterol Levels in Caucasian-Brazilian Patients with Type 2 Diabetes. Metabolic Syndrome and Related Disorders, 12, 16-24.
http://dx.doi.org/10.1089/met.2013.0077 [41] Wang, L., Zhang, B., Li, M., Li, C., Liu, J., Liu, Y., et al. (2014) Association between Single-Nucleotide Polymorphisms in Six Hypertensive Candidate Genes and Hypertension among Northern Han Chinese Individuals. Hypertension Research, 37, 1068-1074. http://dx.doi.org/10.1038/hr.2014.124 [42] Larsen, L.H., Angquist, L., Vimaleswaran, K.S., Hager, J., Viguerie, N., Loos, R.J., et al. (2012) Analyses of Single Nucleotide Polymorphisms in Selected Nutrient-Sensitive Genes in Weight-Regain Prevention: The DIOGENES Study. American Journal of Clinical Nutrition, 95, 1254-1260.
http://dx.doi.org/10.3945/ajcn.111.016543 [43] Catalioto, R.M., Valenti, C., Liverani, L., Giuliani, S. and Maggi, C.A. (2013) Characterization of a Novel Proinflammatory Effect Mediated by BK and the Kinin B? Receptor in Human Preadipocytes. Biochemical Pharmacology, 86, 508-520. http://dx.doi.org/10.1016/j.bcp.2013.06.005 [44] Mori, M.A., Araújo, R.C., Reis, F.C., Sgai, D.G., Fonseca, R.G., Barros, C.C., et al. (2008) Kinin B1 Receptor Deficiency Leads to Leptin Hypersensitivity and Resistance to Obesity. Diabetes, 57, 1491-1500. http://dx.doi.org/10.2337/db07-1508 [45] Puthucheary, Z., Skipworth, J.R., Rawal, J., Loosemore, M., Van Someren, K. and Montgomery, H.E. (2011) The ACE Gene and Human Performance: 12 Years On. Sports Medicine, 41, 433-448.
http://dx.doi.org/10.2165/11588720-000000000-00000 [46] Saunders C.J., Xenophontos, S.L., Cariolou, M.A., Anastassiades, L.C., Noakes, T.D. and Collins, M. (2006) The Bradykinin β2 Receptor (BDKRB2) and Endothelial Nitric Oxide Synthase 3 (NOS3) Genes and Endurance Performance during Ironman Triathlons. Human Molecular Genetics, 15, 979-987.
http://dx.doi.org/10.1093/hmg/ddl014 [47] Li, Y.Y., Zhang, H., Xu, J., Qian, Y., Lu, X.Z., Yang, B., et al. (2012) Bradykinin β2 Receptor-58T/C Gene Polymorphism and Essential Hypertension: A Meta-Analysis. PLoS ONE, 7, e43068.
http://dx.doi.org/10.1371/journal.pone.0043068 [48] Qadri, F., H?user, W., J?hren, O. and Dominiak, P. (2002) Kinin B1 and B2 Receptor mRNA Expression in the Hypothalamus of Spontaneously Hypertensive Rats. Canadian Journal of Physiology and Pharmacology, 80, 258-263. http://dx.doi.org/10.1139/y02-051 [49] Abe, K.C., Mori, M.A. and Pesquero, J.B. (2007) Leptin Deficiency Leads to the Regulation of Kinin Receptors Expression in Mice. Regulatory Peptides, 138, 56-58.
http://dx.doi.org/10.1016/j.regpep.2006.11.018 [50] Hettinger, U., Lukasova, M., Lewicka, S. and Hilgenfeldt, U. (2002) Regulatory Effects of Salt Diet on Renal Renin-Angiotensin-Aldosterone, and Kallikrein-Kinin Systems. International Immunopharmacology, 2, 1975-1980. http://dx.doi.org/10.1016/S1567-5769(02)00163-7 [51] Alves, C.R., Alves, G.B., Pereira, A.C., Trombetta, I.C., Dias, R.G., Mota, G.F., et al. (2013) Vascular Reactivity and ACE Activity Response to Exercise Training Are Modulated by the +9/?9 Bradykinin B? Receptor Gene Functional Polymorphism. Physiological Genomics, 45, 487-492.
http://dx.doi.org/10.1152/physiolgenomics.00065.2012 [52] Zhou, J.B., Liu, C., Niu, W.Y., Xin, Z., Yu, M., Feng, J.P., et al. (2012) Contributions of Renin-Angiotensin System-Related Gene Interactions to Obesity in a Chinese Population. PLoS ONE, 7, e42881.
http://dx.doi.org/10.1371/journal.pone.0042881 [53] Gu, D., Zhao, Q., Kelly, T.N., Hixson, J.E., Rao, D.C., Cao, J., et al. (2012) The Role of the Kallikrein-Kinin System Genes in the Salt Sensitivity of Blood Pressure: The GenSalt Study. American Journal of Epidemiology, 176, S72-S80. http://dx.doi.org/10.1093/aje/kws277 [54] Montasser, M.E., Gu, D., Chen, J., Shimmin, L.C., Gu, C., Kelly, T.N., et al. (2011) Interactions of Genetic Variants with Physical Activity Are Associated with Blood Pressure in Chinese: The GenSalt Study. American Journal of Hypertension, 24, 1035-1040. http://dx.doi.org/10.1038/ajh.2011.97 [55] Srinivasan, V., Ohta, Y., Espino, J., Pariente, J.A., Rodriguez, A.B., Mohamed, M., et al. (2013) Metabolic Syndrome, Its Pathophysiology and the Role of Melatonin. Recent Patents on Endocrine Metabolic & Immune Drug Discovery, 7, 11-25. http://dx.doi.org/10.2174/187221413804660953 [56] Ekmekcioglu, C. (2006) Melatonin Receptors in Humans: Biological Role and Clinical Relevance. Biomedicine & Pharmacotherapy, 60, 97-108. http://dx.doi.org/10.1016/j.biopha.2006.01.002 [57] Koziróg, M., Poliwczak, A.R., Duchnowicz, P., Koter-Michalak, M., Sikora, J. and Broncel, M. (2011) Melatonin treatment Improves Blood Pressure, Lipid Profile, and Parameters of Oxidative Stress in Patients with Metabolic Syndrome. Journal of Pineal Research, 50, 261-266.
http://dx.doi.org/10.1111/j.1600-079X.2010.00835.x [58] Xia, Q., Chen, Z.X., Wang, Y.C., Ma, Y.S., Zhang, F., Che, W., et al. (2012) Association between the Melatonin Receptor 1B Gene Polymorphism on the Risk of Type 2 Diabetes, Impaired Glucose Regulation: A Meta-Analysis. PLoS ONE, 7, e50107. http://dx.doi.org/10.1371/journal.pone.0050107 [59] Huber, M., Treszl, A., Reibis, R., Teichmann, C., Zergibel, I., Bolbrinker, J., et al. (2013) Genetics of Melatonin Receptor Type 2 Is Associated with Left Ventricular Function in Hypertensive Patients Treated According to Guidelines. European Journal of Internal Medicine, 24, 650-655.
http://dx.doi.org/10.1016/j.ejim.2013.03.015 [60] Yang, J., Liu, J., Liu, J., Li, W., Li, X., He, Y., et al. (2014) Genetic Association Study with Metabolic Syndrome and Metabolic-Related Traits in a Cross-Sectional Sample and a 10-Year Longitudinal Sample of Chinese Elderly Population. PLoS ONE, 9, e100548. http://dx.doi.org/10.1371/journal.pone.0100548 [61] Holzapfel, C., Siegrist, M., Rank, M., Langhof, H., Grallert, H., Baumert, J., et al. (2011) Association of a MTNR1B gene Variant with Fasting Glucose and HOMA-B in Children and Adolescents with High BMI-SDS. European Journal of Endocrinology, 164, 205-212. http://dx.doi.org/10.1530/EJE-10-0588 [62] Mirzaei, K., Xu, M., Qi, Q., de Jonge, L., Bray, G.A., Sacks, F., et al. (2014) Variants in Glucose- and Circadian rhythm-Related Genes Affect the Response of Energy Expenditure to Weight-Loss Diets: The POUNDS LOST Trial. American Journal of Clinical Nutrition, 99, 392-399.
http://dx.doi.org/10.3945/ajcn.113.072066
[1] World Health Organization (WHO) (2009) Global Health Risks: Mortality and Burden of Disease Attributable to Selected Major Risks. WHO Press, Geneva. [2] Global Burden of Metabolic Risk Factors for Chronic Diseases Collaboration (2014) Cardiovascular Disease, Chronic Kidney Disease, and Diabetes Mortality Burden of Cardiometabolic Risk Factors from 1980 to 2010: A Comparative Risk Assessment. The Lancet Diabetes & Endocrinology, 2, 634-647.
http://dx.doi.org/10.1016/S2213-8587(14)70102-0 [3] Kearney, P.M., Whelton, M., Reynolds, K,, Muntner, P., Whelton, P.K. and He, J. (2005) Global Burden of Hypertension: Analysis of Worldwide Data. The Lancet, 365, 217-223. http://dx.doi.org/10.1016/S0140-6736(05)70151-3 [4] Brasil. Ministério da Saúde. Secretaria de Vigilancia em Saúde. (2014) Vigitel Brazil 2013: Protective and Risk Factors for Chronic Diseases by Telephone Survey. Ministério da Saúde, Secretaria de Vigilancia em Saúde. Ministério da Saúde, Brasília. [5] Lee, I.M., Shiroma, E.J., Lobelo, F., Puska, P., Blair, S.N. and Katzmarzyk, P.T., Lancet Physical Activity Series Working Group (2012) Effect of Physical Inactivity on Major Non-Communicable Diseases Worldwide: An Analysis of Burden of Disease and Life Expectancy. The Lancet, 380, 219-229.
http://dx.doi.org/10.1016/S0140-6736(12)61031-9 [6] Pischon, T., Boeing, H., Hoffmann, K., Bergmann, M., Schulze, M.B., Overvad, K., et al. (2008) General and Abdominal Adiposity and Risk of Death in Europe. New England Journal of Medicine, 359, 2105-2120. http://dx.doi.org/10.1056/NEJMoa0801891 [7] Kelly, T., Yang, W., Chen, C.S., Reynolds, K. and He, J. (2008) Global Burden of Obesity in 2005 and Projections to 2030. International Journal of Obesity (Lond), 32, 1431-1437.
http://dx.doi.org/10.1038/ijo.2008.102 [8] Beevers, G., Lip, G.Y.H. and O’Brien, E. (2001) ABC of Hypertension: The Pathophysiology of Hypertension. BMJ, 322, 912-916. http://dx.doi.org/10.1136/bmj.322.7291.912 [9] Sanjuliani, A.F. (2002) Pathophysiology of Hypertension: Useful Theoretical Concepts for Clinical Practice. Revista SOCERJ, 15, 210-218. [10] Carvalho, J.J., Baruzzi, R.G., Howard, P.F., Poulter, N., Alpers, M.P., Franco, L.J., et al. (1989) Blood Pressure in Four Remote Populations in the INTERSALT Study. Hypertension, 14, 238-246.
http://dx.doi.org/10.1161/01.HYP.14.3.238 [11] Schlaich, M.P., Klingbeil, A.U., Jacobi, J., Delles, C., Schneider, M.P., Schmidt, B.M., et al. (2002) Altered Aldosterone Response to Salt Intake and Angiotensin II Infusion in Young Normotensive Men with Parental History of Arterial Hypertension. Journal of Hypertension, 20, 117-124.
http://dx.doi.org/10.1097/00004872-200201000-00017 [12] Campos, L.A., Cipolla-Neto, J., Amaral, F.G., Michelini, L.C., Bader, M. and Baltatu, O.C. (2013) The Angiotensin-Melatonin Axis. International Journal of Hypertension, 2013, Article ID: 521783. [13] Francischetti, E.A. and Genelhu, V.A. (2007) Obesity-Hypertension: An Ongoing Pandemic. International Journal of Clinical Practice, 61, 269-280. http://dx.doi.org/10.1111/j.1742-1241.2006.01262.x [14] Nielsen, S., Guo, Z., Johnson, C.M., Hensrud, D.D. and Jensen, M.D. (2004) Splanchnic Lipolysis in Human Obesity. Journal of Clinical Investigation, 113, 1582-1588. http://dx.doi.org/10.1172/JCI21047 [15] Hall, J.E., da Silva, A.A., do Carmo, J.M., Dubinion, J., Hamza, S., Munusamy, S., et al. (2010) Obesity-Induced Hypertension: Role of Sympathetic Nervous System, Leptin, and Melanocortins. Journal of Biological Chemistry, 285, 17271-17276. http://dx.doi.org/10.1074/jbc.R110.113175 [16] Miall, W.E. and Oldham, P.D. (1963) The Hereditary Factor in Arterial Blood-Pressure. BMJ, 1, 75-80. http://dx.doi.org/10.1136/bmj.1.5323.75 [17] Ehret, G.B. and Caulfield, M.J. (2013) Genes for Blood Pressure: An Opportunity to Understand Hypertension. European Heart Journal, 34, 951-961. http://dx.doi.org/10.1093/eurheartj/ehs455 [18] Bauman, A.E., Reis, R.S., Sallis, J.F., Wells, J.C., Loos, R.J. and Martin, B.W., Lancet Physical Activity Series Working Group (2012) Correlates of Physical Activity: Why Are Some People Physically Active and Others Not? Lancet, 380, 258-271. http://dx.doi.org/10.1016/S0140-6736(12)60735-1 [19] Klingberg, F. and Klengel, S. (1993) Lesions in Four Parts of the Basal Forebrain Change Basic Behavior in Rats. NeuroReport, 4, 639-642. http://dx.doi.org/10.1097/00001756-199306000-00009 [20] Simonen, R.L., Perusse, L., Rankinen, T., Rice, T., Rao, D.C. and Bouchard, C. (2002) Familial Aggregation of Physical Activity Levels in the Quebec Family Study. Medicine & Science in Sports & Exercise, 34, 1137-1142. http://dx.doi.org/10.1097/00005768-200207000-00014 [21] Aaltonen, S., Ortega-Alonso, A., Kujala, U.M. and Kaprio, J. (2010) A Longitudinal Study on Genetic and Environmental Influences on Leisure Time Physical Activity in the Finnish Twin Cohort. Twin Research and Human Genetics, 13, 475-481. http://dx.doi.org/10.1375/twin.13.5.475 [22] Ekelund, U., Brage, S., Besson, H., Sharp, S. and Wareham, N.J. (2008) Time Spent Being Sedentary and Weight Gain in Healthy Adults: Reverse or Bidirectional Causality? American Journal of Clinical Nutrition, 88, 612-617. [23] Metcalf, B.S., Hosking, J., Jeffery, A.N., Voss, L.D., Henley, W. and Wilkin, T.J. (2011) Fatness Leads to Inactivity, but Inactivity Does Not Lead to Fatness: A Longitudinal Study in Children. Archives of Disease in Childhood, 96, 942-947. http://dx.doi.org/10.1136/adc.2009.175927 [24] Allison, D.B., Faith, M.S. and Nathan, J.S. (1996) Risch’s Lambda Values for Human Obesity. International Journal of Obesity and Related Metabolic Disorders, 20, 990-999. [25] Bouchard, C. (2008) Gene-Environment Interactions in the Etiology of Obesity: Defining the Fundamentals. Obesity, 16, S5-S10. http://dx.doi.org/10.1038/oby.2008.528 [26] Manolio, T.A. (2010) Genomewide Association Studies and Assessment of the Risk of Disease. New England Journal of Medicine, 363, 166-176. http://dx.doi.org/10.1056/NEJMra0905980 [27] Chorostowska-Wynimko, J. (2002) Mechanism of B2-Agonists Action and Safety Aspects. Polski Merkuriusz Lekarski, 12, 441-444. [28] Snyder, E.M., Johnson, B.D. and Joyner, M.J. (2008) Genetics of β2-Adrenergic Receptors and the Cardiopulmonary Response to Exercise. Exercise and Sport Sciences Reviews, 2, 98-105.
http://dx.doi.org/10.1097/JES.0b013e318168f276 [29] Balligand, J.L. (2013) β3-Adrenoreceptors in Cardiovascular Diseases: New Roles for an “Old” Receptor. Current Drug Delivery, 10, 64-66. http://dx.doi.org/10.2174/1567201811310010011 [30] Zhang, H., Wu, J. and Yu, L. (2014) Association of Gln27Glu and Arg16Gly Polymorphisms in β2-Adrenergic Receptor Gene with Obesity Susceptibility: A Meta-Analysis. PLoS ONE, 9, e100489.
http://dx.doi.org/10.1371/journal.pone.0100489 [31] Snyder, E.M., Beck, K.C., Dietz, N.M., Eisenach, J.H., Joyner, M.J., Turner, S.T., et al. (2006) Arg16Gly Polymorphism of the β2-Adrenergic Receptor is Associated with Differences in Cardiovascular Function at Rest and during Exercise in Humans. The Journal of Physiology, 571, 121-30.
http://dx.doi.org/10.1113/jphysiol.2005.098558 [32] Sipil?inen, R., Uusitupa, M., Heikkinen, S., Rissanen, A. and Laakso, M. (1997) Polymorphism of the β3-Adrenergic Receptor Gene Affects Basal Metabolic Rate in Obese Finns. Diabetes, 46, 77-80.
http://dx.doi.org/10.2337/diabetes.46.1.77 [33] Villares, S.M., Mancini, M.C., Gomez, S., Charf, A.M., Frazzatto, E. and Halpern, A. (2000) Association between Polymorphism Gln27Glu of β2-Adrenergic Receptor and Hypertension in Morbid Obese. Arquivos Brasileiros de Endo crinologia e Metabologia, 44, 72-80. [34] Rauhio, A., Uusi-Rasi, K., Nikkari, S.T., Kannus, P., Siev?nen, H. and Kunnas, T. (2013) Association of the FTO and ADRB2 Genes with Body Composition and Fat Distribution in Obese Women. Maturitas, 76, 165-171. http://dx.doi.org/10.1016/j.maturitas.2013.07.004 [35] Macho-Azcarate, T., Marti, A., González, A., Martinez, J.A. and Iba?ez, J. (2002) Gln27Glu Polymorphism in the beta2 Adrenergic Receptor Gene and Lipid Metabolism during Exercise in Obese Women. International Journal of Obesity and Related Metabolic Disorders, 26, 1434-1441.
http://dx.doi.org/10.1038/sj.ijo.0802129 [36] Lagou, V., Liu, G., Zhu, H., Stallmann-Jorgensen, I.S., Gutin, B., Dong, Y., et al. (2011) Lifestyle and Socioeconomic-Status Modify the Effects of ADRB2 and NOS3 on Adiposity in European-American and African-American Adolescents. Obesity, 19, 595-603. http://dx.doi.org/10.1038/oby.2010.224 [37] Ochoa, M.C., Moreno-Aliaga, M.J., Martínez-González, M.A., Martínez, J.A. and Marti, A., GENOI Members (2006) TV Watching Modifies Obesity Risk Linked to the 27Glu Polymorphism of the ADRB2 Gene in Girls. International Journal of Pediatric Obesity, 1, 83-88. http://dx.doi.org/10.1080/17477160600650386 [38] Nakashima, H., Omae, K., Nomiyama, T., Yamano, Y., Takebayashi, T. and Sakurai, Y. (2013) Beta-3-Adrenergic Receptor Trp64Arg Polymorphism: Does It Modulate the Relationship between Exercise and Percentage of Body Fat in Young Adult Japanese Males? Environmental Health and Preventive Medicine, 18, 323-329. http://dx.doi.org/10.1007/s12199-012-0325-3 [39] Saliba, L.F., Reis, R.S., Brownson, R.C., Hino, A.A., Tureck, L.V., Valko, C., et al. (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, 15-22.
http://dx.doi.org/10.1590/S1415-47572014000100005 [40] Brondani, L.A., Duarte, G.C., Canani, L.H. and Crispim, D. (2014) The Presence of at Least Three Alleles of the ADRB3 Trp64Arg (C/T) and UCP1-3826A/G Polymorphisms Is Associated with Protection to Overweight/Obesity and with Higher High-Density Lipoprotein Cholesterol Levels in Caucasian-Brazilian Patients with Type 2 Diabetes. Metabolic Syndrome and Related Disorders, 12, 16-24.
http://dx.doi.org/10.1089/met.2013.0077 [41] Wang, L., Zhang, B., Li, M., Li, C., Liu, J., Liu, Y., et al. (2014) Association between Single-Nucleotide Polymorphisms in Six Hypertensive Candidate Genes and Hypertension among Northern Han Chinese Individuals. Hypertension Research, 37, 1068-1074. http://dx.doi.org/10.1038/hr.2014.124 [42] Larsen, L.H., Angquist, L., Vimaleswaran, K.S., Hager, J., Viguerie, N., Loos, R.J., et al. (2012) Analyses of Single Nucleotide Polymorphisms in Selected Nutrient-Sensitive Genes in Weight-Regain Prevention: The DIOGENES Study. American Journal of Clinical Nutrition, 95, 1254-1260.
http://dx.doi.org/10.3945/ajcn.111.016543 [43] Catalioto, R.M., Valenti, C., Liverani, L., Giuliani, S. and Maggi, C.A. (2013) Characterization of a Novel Proinflammatory Effect Mediated by BK and the Kinin B? Receptor in Human Preadipocytes. Biochemical Pharmacology, 86, 508-520. http://dx.doi.org/10.1016/j.bcp.2013.06.005 [44] Mori, M.A., Araújo, R.C., Reis, F.C., Sgai, D.G., Fonseca, R.G., Barros, C.C., et al. (2008) Kinin B1 Receptor Deficiency Leads to Leptin Hypersensitivity and Resistance to Obesity. Diabetes, 57, 1491-1500. http://dx.doi.org/10.2337/db07-1508 [45] Puthucheary, Z., Skipworth, J.R., Rawal, J., Loosemore, M., Van Someren, K. and Montgomery, H.E. (2011) The ACE Gene and Human Performance: 12 Years On. Sports Medicine, 41, 433-448.
http://dx.doi.org/10.2165/11588720-000000000-00000 [46] Saunders C.J., Xenophontos, S.L., Cariolou, M.A., Anastassiades, L.C., Noakes, T.D. and Collins, M. (2006) The Bradykinin β2 Receptor (BDKRB2) and Endothelial Nitric Oxide Synthase 3 (NOS3) Genes and Endurance Performance during Ironman Triathlons. Human Molecular Genetics, 15, 979-987.
http://dx.doi.org/10.1093/hmg/ddl014 [47] Li, Y.Y., Zhang, H., Xu, J., Qian, Y., Lu, X.Z., Yang, B., et al. (2012) Bradykinin β2 Receptor-58T/C Gene Polymorphism and Essential Hypertension: A Meta-Analysis. PLoS ONE, 7, e43068.
http://dx.doi.org/10.1371/journal.pone.0043068 [48] Qadri, F., H?user, W., J?hren, O. and Dominiak, P. (2002) Kinin B1 and B2 Receptor mRNA Expression in the Hypothalamus of Spontaneously Hypertensive Rats. Canadian Journal of Physiology and Pharmacology, 80, 258-263. http://dx.doi.org/10.1139/y02-051 [49] Abe, K.C., Mori, M.A. and Pesquero, J.B. (2007) Leptin Deficiency Leads to the Regulation of Kinin Receptors Expression in Mice. Regulatory Peptides, 138, 56-58.
http://dx.doi.org/10.1016/j.regpep.2006.11.018 [50] Hettinger, U., Lukasova, M., Lewicka, S. and Hilgenfeldt, U. (2002) Regulatory Effects of Salt Diet on Renal Renin-Angiotensin-Aldosterone, and Kallikrein-Kinin Systems. International Immunopharmacology, 2, 1975-1980. http://dx.doi.org/10.1016/S1567-5769(02)00163-7 [51] Alves, C.R., Alves, G.B., Pereira, A.C., Trombetta, I.C., Dias, R.G., Mota, G.F., et al. (2013) Vascular Reactivity and ACE Activity Response to Exercise Training Are Modulated by the +9/?9 Bradykinin B? Receptor Gene Functional Polymorphism. Physiological Genomics, 45, 487-492.
http://dx.doi.org/10.1152/physiolgenomics.00065.2012 [52] Zhou, J.B., Liu, C., Niu, W.Y., Xin, Z., Yu, M., Feng, J.P., et al. (2012) Contributions of Renin-Angiotensin System-Related Gene Interactions to Obesity in a Chinese Population. PLoS ONE, 7, e42881.
http://dx.doi.org/10.1371/journal.pone.0042881 [53] Gu, D., Zhao, Q., Kelly, T.N., Hixson, J.E., Rao, D.C., Cao, J., et al. (2012) The Role of the Kallikrein-Kinin System Genes in the Salt Sensitivity of Blood Pressure: The GenSalt Study. American Journal of Epidemiology, 176, S72-S80. http://dx.doi.org/10.1093/aje/kws277 [54] Montasser, M.E., Gu, D., Chen, J., Shimmin, L.C., Gu, C., Kelly, T.N., et al. (2011) Interactions of Genetic Variants with Physical Activity Are Associated with Blood Pressure in Chinese: The GenSalt Study. American Journal of Hypertension, 24, 1035-1040. http://dx.doi.org/10.1038/ajh.2011.97 [55] Srinivasan, V., Ohta, Y., Espino, J., Pariente, J.A., Rodriguez, A.B., Mohamed, M., et al. (2013) Metabolic Syndrome, Its Pathophysiology and the Role of Melatonin. Recent Patents on Endocrine Metabolic & Immune Drug Discovery, 7, 11-25. http://dx.doi.org/10.2174/187221413804660953 [56] Ekmekcioglu, C. (2006) Melatonin Receptors in Humans: Biological Role and Clinical Relevance. Biomedicine & Pharmacotherapy, 60, 97-108. http://dx.doi.org/10.1016/j.biopha.2006.01.002 [57] Koziróg, M., Poliwczak, A.R., Duchnowicz, P., Koter-Michalak, M., Sikora, J. and Broncel, M. (2011) Melatonin treatment Improves Blood Pressure, Lipid Profile, and Parameters of Oxidative Stress in Patients with Metabolic Syndrome. Journal of Pineal Research, 50, 261-266.
http://dx.doi.org/10.1111/j.1600-079X.2010.00835.x [58] Xia, Q., Chen, Z.X., Wang, Y.C., Ma, Y.S., Zhang, F., Che, W., et al. (2012) Association between the Melatonin Receptor 1B Gene Polymorphism on the Risk of Type 2 Diabetes, Impaired Glucose Regulation: A Meta-Analysis. PLoS ONE, 7, e50107. http://dx.doi.org/10.1371/journal.pone.0050107 [59] Huber, M., Treszl, A., Reibis, R., Teichmann, C., Zergibel, I., Bolbrinker, J., et al. (2013) Genetics of Melatonin Receptor Type 2 Is Associated with Left Ventricular Function in Hypertensive Patients Treated According to Guidelines. European Journal of Internal Medicine, 24, 650-655.
http://dx.doi.org/10.1016/j.ejim.2013.03.015 [60] Yang, J., Liu, J., Liu, J., Li, W., Li, X., He, Y., et al. (2014) Genetic Association Study with Metabolic Syndrome and Metabolic-Related Traits in a Cross-Sectional Sample and a 10-Year Longitudinal Sample of Chinese Elderly Population. PLoS ONE, 9, e100548. http://dx.doi.org/10.1371/journal.pone.0100548 [61] Holzapfel, C., Siegrist, M., Rank, M., Langhof, H., Grallert, H., Baumert, J., et al. (2011) Association of a MTNR1B gene Variant with Fasting Glucose and HOMA-B in Children and Adolescents with High BMI-SDS. European Journal of Endocrinology, 164, 205-212. http://dx.doi.org/10.1530/EJE-10-0588 [62] Mirzaei, K., Xu, M., Qi, Q., de Jonge, L., Bray, G.A., Sacks, F., et al. (2014) Variants in Glucose- and Circadian rhythm-Related Genes Affect the Response of Energy Expenditure to Weight-Loss Diets: The POUNDS LOST Trial. American Journal of Clinical Nutrition, 99, 392-399.
http://dx.doi.org/10.3945/ajcn.113.072066