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Journal of Obesity
Volume 2011, Article ID 609485, 10 pages
http://dx.doi.org/10.1155/2011/609485
Review Article

Relationships of Adrenoceptor Polymorphisms with Obesity

1Nucleus Network, Ltd, Baker IDI Heart and Diabetes Research Institute, 89 Commercial Road, Melbourne, VIC 3004, Australia
2Human Neurotransmitter Laboratory, Baker IDI Heart and Diabetes Research Institute, Melbourne, VIC 3004, Australia

Received 24 November 2010; Accepted 7 February 2011

Academic Editor: Eric Doucet

Copyright © 2011 Kazuko Masuo and Gavin W. Lambert. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. A. H. Mokdad, B. A. Bowman, E. S. Ford, F. Vinicor, J. S. Marks, and J. P. Koplan, “The continuing epidemics of obesity and diabetes in the United States,” The Journal of the American Medical Association, vol. 286, no. 10, pp. 1195–1200, 2001. View at Google Scholar · View at Scopus
  2. C. Heidemann, H. Boeing, T. Pischon, U. Nöthlings, H. G. Joost, and M. B. Schulze, “Association of a diabetes risk score with risk of myocardial infarction, stroke, specific types of cancer, and mortality: a prospective study in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort,” European Journal of Epidemiology, vol. 24, no. 6, pp. 281–288, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  3. K. M. Flegal, B. I. Graubard, D. F. Williamson, and M. H. Gail, “Cause-specific excess deaths associated with underweight, overweight, and obesity,” The Journal of the American Medical Association, vol. 298, no. 17, pp. 2028–2037, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  4. E. Lambert, C. I. Sari, T. Dawood et al., “Sympathetic nervous system activity is associated with obesity-induced subclinical organ damage in young adults,” Hypertension, vol. 56, no. 3, pp. 351–358, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  5. F. Ramsey, A. Ussery-Hall, D. Garcia et al., “Prevalence of selected risk behaviors and chronic diseases: behavioral Risk Factor Surveillance System (BRFSS), 39 steps communities, United States, 2005,” Morbidity and Mortality Weekly Report. Surveillance Summaries/CDC, vol. 57, no. 11, pp. 1–20, 2008. View at Google Scholar
  6. C. L. Ogden, C. D. Fryar, M. D. Carroll, and K. M. Flegal, “Mean body weight, height, and body mass index, United States 1960–2002,” Advance Data, no. 347, pp. 1–17, 2004. View at Google Scholar
  7. A. H. Mokdad, M. K. Serdula, W. H. Dietz, B. A. Bowman, J. S. Marks, and J. P. Koplan, “The spread of the obesity epidemic in the United States, 1991–1998,” The Journal of the American Medical Association, vol. 282, no. 16, pp. 1519–1522, 1999. View at Publisher · View at Google Scholar · View at Scopus
  8. G. W. Lambert, N. E. Straznicky, E. A. Lambert, J. B. Dixon, and M. P. Schlaich, “Sympathetic nervous activation in obesity and the metabolic syndrome—causes, consequences and therapeutic implications,” Pharmacology and Therapeutics, vol. 126, no. 2, pp. 159–172, 2010. View at Publisher · View at Google Scholar · View at PubMed
  9. S. R. Preis, S. J. Hwang, S. Coady et al., “Trends in all-cause and cardiovascular disease mortality among women and men with and without diabetes mellitus in the framingham heart study, 1950 to 2005,” Circulation, vol. 119, no. 13, pp. 1728–1735, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  10. N. E. Straznicky, G. W. Lambert, K. Masuo et al., “Blunted sympathetic neural response to oral glucose in obese subjects with the insulin-resistant metabolic syndrome,” American Journal of Clinical Nutrition, vol. 89, no. 1, pp. 27–36, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  11. K. Masuo, H. Mikami, T. Ogihara, and M. L. Tuck, “Differences in insulin and sympathetic responses to glucose ingestion due to family history of hypertension,” American Journal of Hypertension, vol. 9, no. 8, pp. 739–745, 1996. View at Publisher · View at Google Scholar · View at Scopus
  12. M. Spraul, E. Ravussin, A. M. Fontvieille, R. Rising, D. E. Larson, and E. A. Anderson, “Reduced sympathetic nervous activity. A potential mechanism predisposing to body weight gain,” Journal of Clinical Investigation, vol. 92, no. 4, pp. 1730–1735, 1993. View at Google Scholar · View at Scopus
  13. A. M. Cypess, S. Lehman, G. Williams et al., “Identification and importance of brown adipose tissue in adult humans,” The New England Journal of Medicine, vol. 360, no. 15, pp. 1509–1517, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  14. J. A. Timmons and B. K. Pedersen, “The importance of brown adipose tissue,” The New England Journal of Medicine, vol. 361, no. 4, pp. 415–416, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  15. H. S. Sacks, “The importance of brown adipose tissue,” The New England Journal of Medicine, vol. 361, no. 4, p. 418, 2009. View at Google Scholar · View at Scopus
  16. S. Iwashita, M. Tanida, N. Terui et al., “Direct measurement of renal sympathetic nervous activity in high-fat diet-related hypertensive rats,” Life Sciences, vol. 71, no. 5, pp. 537–546, 2002. View at Publisher · View at Google Scholar · View at Scopus
  17. M. B. Monroe, D. R. Seals, L. F. Shapiro, C. Bell, D. Johnson, and P. Parker-Jones, “Direct evidence for tonic sympathetic support of resting metabolic rate in healthy adult humans,” American Journal of Physiology, vol. 280, no. 5, pp. E740–E744, 2001. View at Google Scholar · View at Scopus
  18. E. E. Blaak, M. A. van Baak, K. P. G. Kempen, and W. H. M. Saris, “Role of α- and β-adrenoceptors in sympathetically mediated thermogenesis,” American Journal of Physiology, vol. 264, no. 1, part 1, pp. E11–E17, 1993. View at Google Scholar · View at Scopus
  19. E. Hagström-Toft, S. Enoksson, E. Moberg, J. Bolinder, and P. Arner, “β-adrenergic regulation of lipolysis and blood flow in human skeletal muscle in vivo,” American Journal of Physiology, vol. 275, no. 6, pp. E909–E916, 1998. View at Google Scholar · View at Scopus
  20. S. Enoksson, M. Talbot, F. Rife, W. V. Tamborlane, R. S. Sherwin, and S. Caprio, “Impaired in vivo stimulation of lipolysis in adipose tissue by selective β2-adrenergic agonist in obese adolescent girls,” Diabetes, vol. 49, no. 12, pp. 2149–2153, 2000. View at Google Scholar · View at Scopus
  21. K. Masuo, H. Mikami, T. Ogihara, and M. L. Tuck, “Familial hypertension, insulin, sympathetic activity, and blood pressure elevation,” Hypertension, vol. 32, no. 1, pp. 96–100, 1998. View at Google Scholar · View at Scopus
  22. K. Masuo, H. Mikami, T. Ogihara, and M. L. Tuck, “Familial obesity, sympathetic activation and blood pressure level,” Blood Pressure, vol. 10, no. 4, pp. 199–204, 2001. View at Publisher · View at Google Scholar · View at Scopus
  23. J. Cui, J. L. Hopper, and S. B. Harrap, “Genes and family environment explain correlations between blood pressure and body mass index,” Hypertension, vol. 40, no. 1, pp. 7–12, 2002. View at Publisher · View at Google Scholar · View at Scopus
  24. K. Masuo, T. Katsuya, Y. Fu, H. Rakugi, T. Ogihara, and M. L. Tuck, “β2- and β3-adrenergic receptor polymorphisms are related to the onset of weight gain and blood pressure elevation over 5 years,” Circulation, vol. 111, no. 25, pp. 3429–3434, 2005. View at Publisher · View at Google Scholar · View at PubMed
  25. A. C. Pereira, M. S. Floriano, G. F. A. Mota et al., “β2 adrenoceptor functional gene variants, obesity, and blood pressure level interactions in the general population,” Hypertension, vol. 42, no. 4, pp. 685–692, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  26. K. Masuo, T. Katsuya, H. Kawaguchi et al., “Rebound weight gain as associated with high plasma norepinephrine levels that are mediated through polymorphisms in the β2-adrenoceptor,” American Journal of Hypertension, vol. 18, no. 11, pp. 1508–1516, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  27. K. Masuo, T. Katsuya, Y. Fu, H. Rakugi, T. Ogihara, and M. L. Tuck, “β2-adrenoceptor polymorphisms relate to insulin resistance and sympathetic overactivity as early markers of metabolic disease in nonobese, normotensive individuals,” American Journal of Hypertension, vol. 18, no. 7, pp. 1009–1014, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  28. K. Masuo, T. Katsuya, H. Kawaguchi et al., “β2-adrenoceptor polymorphisms relate to obesity through blunted leptin-mediated sympathetic activation,” American Journal of Hypertension, vol. 19, no. 10, pp. 1084–1091, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  29. H. Kawaguchi, K. Masuo, T. Katsuya et al., “β2- and β3-adrenoceptor polymorphisms relate to subsequent weight gain and blood pressure elevation in obese normotensive individuals,” Hypertension Research, vol. 29, no. 12, pp. 951–959, 2006. View at Publisher · View at Google Scholar · View at PubMed
  30. T. J. Maxwell, M. M. Ameyaw, S. Pritchard et al., “Beta-2 adrenergic receptor genotypes and haplotypes in different ethnic groups,” International Journal of Molecular Medicine, vol. 16, no. 4, pp. 573–580, 2005. View at Google Scholar · View at Scopus
  31. N. E. Straznicky, N. Eikelis, E. A. Lambert, and M. D. Esler, “Mediators of sympathetic activation in metabolic syndrome obesity,” Current Hypertension Reports, vol. 10, no. 6, pp. 440–447, 2008. View at Publisher · View at Google Scholar · View at Scopus
  32. J. L. González Sánchez, A. M. Proenza, M. T. Martínez Larrad et al., “The glutamine 27 glutamic acid polymorphism of the β2-adrenoceptor gene is associated with abdominal obesity and greater risk of impaired glucose tolerance in men but not in women: a population-based study in Spain,” Clinical Endocrinology, vol. 59, no. 4, pp. 476–481, 2003. View at Publisher · View at Google Scholar
  33. N. E. Straznicky, E. A. Lambert, G. W. Lambert, K. Masuo, M. D. Esler, and P. J. Nestel, “Effects of dietary weight loss on sympathetic activity and cardiac risk factors associated with the metabolic syndrome,” Journal of Clinical Endocrinology & Metabolism, vol. 90, no. 11, pp. 5998–6005, 2005. View at Publisher · View at Google Scholar · View at PubMed
  34. L. Landsberg, “Insulin-mediated sympathetic stimulation: role in the pathogenesis of obesity-related hypertension (or, how insulin affects blood pressure, and why),” Journal of Hypertension, vol. 19, no. 3, pp. 523–528, 2001. View at Publisher · View at Google Scholar · View at Scopus
  35. E. A. Anderson, R. P. Hoffman, T. W. Balon, C. A. Sinkey, and A. L. Mark, “Hyperinsulinemia produces both sympathetic neural activation and vasodilation in normal humans,” Journal of Clinical Investigation, vol. 87, no. 6, pp. 2246–2252, 1991. View at Google Scholar · View at Scopus
  36. E. Ferrannini, “Physiological and metabolic consequences of obesity,” Metabolism, vol. 44, no. 9, supplement 3, pp. 15–17, 1995. View at Google Scholar · View at Scopus
  37. J.-P. Montani, V. Antic, Z. Yang, and A. Dulloo, “Pathways from obesity to hypertension: from the perspective of a vicious triangle,” International Journal of Obesity, vol. 26, supplement 2, pp. S28–S38, 2002. View at Google Scholar
  38. C. L. Gentile, J. S. Orr, B. M. Davy, and K. P. Davy, “Modest weight gain is associated with sympathetic neural activation in nonobese humans,” American Journal of Physiology, vol. 292, no. 5, pp. R1834–R1838, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  39. M. J. Barnes, K. Lapanowski, A. Conley, J. A. Rafols, K. L. C. Jen, and J. C. Dunbar, “High fat feeding is associated with increased blood pressure, sympathetic nerve activity and hypothalamic mu opioid receptors,” Brain Research Bulletin, vol. 61, no. 5, pp. 511–519, 2003. View at Publisher · View at Google Scholar · View at Scopus
  40. K. Masuo, H. Mikami, T. Ogihara, and M. L. Tuck, “Weight reduction and pharmacologic treatment in obese hypertensives,” American Journal of Hypertension, vol. 14, no. 6, part 1, pp. 530–538, 2001. View at Publisher · View at Google Scholar · View at Scopus
  41. B. Andersson, M. Elam, B. G. Wallin, P. Bjorntorp, and O. K. Andersson, “Effect of energy-restricted diet on sympathetic muscle nerve activity in obese women,” Hypertension, vol. 18, no. 6, pp. 783–789, 1991. View at Google Scholar · View at Scopus
  42. N. E. Straznicky, E. A. Lambert, G. W. Lambert, K. Masuo, M. D. Esler, and P. J. Nestel, “Effects of dietary weight loss on sympathetic activity and cardiac risk factors associated with the metabolic syndrome,” Journal of Clinical Endocrinology & Metabolism, vol. 90, no. 11, pp. 5998–6005, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  43. K. Masuo, H. Mikami, T. Ogihara, and M. L. Tuck, “Differences in mechanisms between weight loss-sensitive and -resistant blood pressure reduction in obese subjects,” Hypertension Research, vol. 24, no. 4, pp. 371–376, 2001. View at Publisher · View at Google Scholar · View at Scopus
  44. M. L. Tuck, J. R. Sowers, and L. Dornfeld, “Reductions in plasma catecholamines and blood pressure during weight loss in obese subjects,” Acta Endocrinologica, vol. 102, no. 2, pp. 252–257, 1983. View at Google Scholar · View at Scopus
  45. G. Grassi, G. Seravalle, M. Colombo et al., “Body weight reduction, sympathetic nerve traffic, and arterial baroreflex in obese normotensive humans,” Circulation, vol. 97, no. 20, pp. 2037–2042, 1998. View at Google Scholar · View at Scopus
  46. L. Landsberg, “Diet, obesity and hypertension: an hypothesis involving insulin, the sympathetic nervous system, and adaptive thermogenesis,” The Quarterly Journal of Medicine, vol. 61, no. 236, pp. 1081–1090, 1986. View at Google Scholar · View at Scopus
  47. L. Landsberg and J. B. Young, “Diet and the sympathetic nervous system: relationship to hypertension,” International Journal of Obesity, vol. 5, supplement 1, pp. 79–91, 1981. View at Google Scholar · View at Scopus
  48. L. Landsberg and D. R. Krieger, “Obesity, metabolism, and the sympathetic nervous system,” American Journal of Hypertension, vol. 2, no. 3, pp. 125S–132S, 1989. View at Google Scholar · View at Scopus
  49. S. Julius, M. Valentini, and P. Palatini, “Overweight and hypertension: a 2-way street?” Hypertension, vol. 35, no. 3, pp. 807–813, 2000. View at Google Scholar · View at Scopus
  50. K. O'Dea, M. Esler, and P. Leonard, “Noradrenaline turnover during under- and over-eating in normal weight subjects,” Metabolism, vol. 31, no. 9, pp. 896–899, 1982. View at Google Scholar
  51. K. Masuo, H. Kawaguchi, H. Mikami, T. Ogihara, and M. L. Tuck, “Serum uric acid and plasma norepinephrine concentrations predict subsequent weight gain and blood pressure elevation,” Hypertension, vol. 42, no. 4, pp. 474–480, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  52. K. Masuo, H. Mikami, T. Ogihara, and M. L. Tuck, “Weight gain-induced blood pressure elevation,” Hypertension, vol. 35, no. 5, pp. 1135–1140, 2000. View at Google Scholar · View at Scopus
  53. M. Valentini, S. Julius, P. Palatini et al., “Attenuation of haemodynamic, metabolic and energy expenditure responses to isoproterenol in patients with hypertension,” Journal of Hypertension, vol. 22, no. 10, pp. 1999–2006, 2004. View at Publisher · View at Google Scholar · View at Scopus
  54. Y. T. Yang and M. A. McElligott, “Multiple actions of β-adrenergic agonists on skeletal muscle and adipose tissue,” Biochemical Journal, vol. 261, no. 1, pp. 1–10, 1989. View at Google Scholar · View at Scopus
  55. V. Large, L. Hellstrom, S. Reynisdottir et al., “Human beta-2 adrenoceptor gene polymorphisms are highly frequent in obesity and associate with altered adipocyte beta-2 adrenoceptor function,” Journal of Clinical Investigation, vol. 100, no. 12, pp. 3005–3013, 1997. View at Google Scholar
  56. O. Ukkola, A. Tremblay, and C. Bouchard, “Beta-2 adrenergic receptor variants are associated with subcutaneous fat accumulation in response to long-term overfeeding,” International Journal of Obesity, vol. 25, no. 11, pp. 1604–1608, 2001. View at Publisher · View at Google Scholar · View at PubMed
  57. S. Enoksson, E. Hagström-Toft, J. Nordahl et al., “Marked reutilization of free fatty acids during activated lipolysis in human skeletal muscle,” Journal of Clinical Endocrinology & Metabolism, vol. 90, no. 2, pp. 1189–1195, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  58. S. M. Echwald, T. I. A. Sørensen, A. Tybjærg-Hansen, T. Andersen, and O. Pedersen, “Gln27Glu variant of the human β2-adrenoreceptor gene is not associated with early-onset obesity in Danish men,” Diabetes, vol. 47, no. 10, pp. 1657–1658, 1998. View at Publisher · View at Google Scholar · View at Scopus
  59. L. Hellström, V. Large, S. Reynisdottir, H. Wahrenberg, and P. Arner, “The different effects of a Gln27Glu β2-adrenoceptor gene polymorphism on obesity in males and in females,” Journal of Internal Medicine, vol. 245, no. 3, pp. 253–259, 1999. View at Publisher · View at Google Scholar · View at Scopus
  60. I. J. Dionne, M. J. Garant, A. A. Nolan et al., “Association between obesity and a polymorphism in the β1-adrenoceptor gene (Gly389Arg ADRB1) in Caucasian women,” International Journal of Obesity, vol. 26, no. 5, pp. 633–639, 2002. View at Publisher · View at Google Scholar · View at PubMed
  61. J. Tafel, I. Branscheid, B. Skwarna et al., “Variants in the human β1-, β2- and β3-adrenergic receptor genes are not associated with morbid obesity in children and adolescents,” Diabetes, Obesity & Metabolism, vol. 6, no. 6, pp. 452–455, 2004. View at Publisher · View at Google Scholar · View at PubMed
  62. Y. Linné, I. Dahlman, and J. Hoffstedt, “β1-adrenoceptor gene polymorphism predicts long-term changes in body weight,” International Journal of Obesity, vol. 29, no. 5, pp. 458–462, 2005. View at Publisher · View at Google Scholar · View at PubMed
  63. A. P. Gjesing, G. Andersen, A. Albrechtsen et al., “Studies of associations between the Arg389Gly polymorphism of the β1-adrenergic receptor gene (ADRB1) and hypertension and obesity in 7677 Danish white subjects,” Diabetic Medicine, vol. 24, no. 4, pp. 392–397, 2007. View at Publisher · View at Google Scholar · View at PubMed
  64. S. Nonen, I. Yamamoto, J. Liu et al., “Adrenergic β1 receptor polymorphism (Ser49gly) is associated with obesity in type II diabetic patients,” Biological & Pharmaceutical Bulletin, vol. 31, no. 2, pp. 295–298, 2008. View at Publisher · View at Google Scholar
  65. M. Rasmussen, A. Belza, T. Almdal et al., “Change in β1-adrenergic receptor protein concentration in adipose tissue correlates with diet-induced weight loss,” Clinical Science, vol. 108, no. 4, pp. 323–329, 2005. View at Publisher · View at Google Scholar · View at PubMed
  66. M. Ryden, J. Hoffstedt, P. Eriksson, S. Bringman, and P. Arner, “The Arg389Gly β1-adrenergic receptor gene polymorphism and human fat cell lipolysis,” International Journal of Obesity, vol. 25, no. 11, pp. 1599–1603, 2001. View at Publisher · View at Google Scholar · View at PubMed
  67. K. Bengtsson, O. Melander, M. Orho-Melander et al., “Polymorphism in the β1-adrenergic receptor gene and hypertension,” Circulation, vol. 104, no. 2, pp. 187–190, 2001. View at Google Scholar
  68. L. M. Humma, B. J. Puckett, H. E. Richardson et al., “Effects of beta-adrenoceptor genetic polymorphisms on resting hemodynamics in patients undergoing diagnostic testing for ischemia,” American Journal of Cardiology, vol. 88, no. 9, pp. 1034–1037, 2001. View at Publisher · View at Google Scholar
  69. B. Kortner, A. Wolf, D. Wendt, U. Beisiegel, and D. Evans, “Lack of association between a human β-2 adrenoceptor gene polymorphism (gln27glu) and morbid obesity,” International Journal of Obesity, vol. 23, no. 10, pp. 1099–1100, 1999. View at Google Scholar
  70. N. R. Stob, D. R. Seals, J. Jensen et al., “Increased thermogenic responsiveness to intravenous β-adrenergic stimulation in habitually exercising humans is not related to skeletal muscle β2-adrenergic receptor density,” Experimental Physiology, vol. 92, no. 5, pp. 823–830, 2007. View at Publisher · View at Google Scholar · View at PubMed
  71. A. Meirhaeghe, N. Helbecque, D. Cottel, and P. Amouyel, “Impact of polymorphisms of the human β2-adrenoceptor gene on obesity in a French population,” International Journal of Obesity, vol. 24, no. 3, pp. 382–387, 2000. View at Google Scholar
  72. K. Bengtsson, M. Orho-Melander, O. Melander et al., “β2-adrenergic receptor gene variation and hypertension in subjects with type 2 diabetes,” Hypertension, vol. 37, no. 5, pp. 1303–1308, 2001. View at Google Scholar
  73. H. Jiao, I. Dahlman, P. Eriksson, J. Kere, and P. Arner, “A common β2-adrenoceptor gene haplotype protects against obesity in Swedish women,” Obesity Research, vol. 13, no. 10, pp. 1645–1650, 2005. View at Google Scholar
  74. A. Petrone, S. Zavarella, G. Iacobellis et al., “Association of β2 adrenergic receptor polymorphisms and related haplotypes with triglyceride and LDL-cholesterol levels,” European Journal of Human Genetics, vol. 14, no. 1, pp. 94–100, 2006. View at Publisher · View at Google Scholar · View at PubMed
  75. A. P. Gjesing, T. Sparsø, K. Borch-Johnsen et al., “No consistent effect of ADRB2 haplotypes on obesity, hypertension and quantitative traits of body fatness and blood pressure among 6,514 adult danes,” PLoS One, vol. 4, no. 9, Article ID e7206, 2009. View at Publisher · View at Google Scholar · View at PubMed
  76. P. Eriksson, I. Dahlman, M. Ryden, J. Hoffstedt, and P. Arner, “Relationship between β-2 adrenoceptor gene haplotypes and adipocyte lipolysis in women,” International Journal of Obesity, vol. 28, no. 2, pp. 185–190, 2004. View at Google Scholar
  77. S. A. Green, J. Turki, M. Innis, and S. B. Liggett, “Amino-terminal polymorphisms of the human β2-adrenergic receptor impart distinct agonist-promoted regulatory properties,” Biochemistry, vol. 33, no. 32, pp. 9414–9419, 1994. View at Google Scholar
  78. V. Dishy, G. G. Sofowora, H.-G. Xie et al., “The effect of common polymorphisms of the β2-adrenergic receptor on agonist-mediated vascular desensitization,” The New England Journal of Medicine, vol. 345, no. 14, pp. 1030–1035, 2001. View at Publisher · View at Google Scholar · View at PubMed
  79. G. Gratze, J. Fortin, R. Labugger et al., “β-2 adrenergic receptor variants affect resting blood pressure and agonist-induced vasodilation in young adult Caucasians,” Hypertension, vol. 33, no. 6, pp. 1425–1430, 1999. View at Google Scholar
  80. B. D. Hoit, D. P. Suresh, L. Craft, R. A. Walsh, and S. B. Liggett, “β2-adrenergic receptor polymorphisms at amino acid 16 differentially influence agonist-stimulated blood pressure and peripheral blood flow in normal individuals,” American Heart Journal, vol. 139, no. 3, pp. 537–542, 2000. View at Google Scholar
  81. K. Leineweber, “Beta-adrenergic receptor polymorphism in human cardiovascular disease,” Annals of Medicine, vol. 36, supplement 1, pp. 64–69, 2004. View at Publisher · View at Google Scholar
  82. C. Bell, N. R. Stob, and D. R. Seals, “Thermogenic responsiveness to nonspecific β-adrenergic stimulation is not related to genetic variation in codon 16 of the β2-adrenergic receptor,” American Journal of Physiology, vol. 290, no. 4, pp. E703–E707, 2006. View at Publisher · View at Google Scholar · View at PubMed
  83. K. Clement, C. Vaisse, B. S. J. Manning et al., “Genetic variation in the β3-adrenergic receptor and an increased capacity to gain weight in patients with morbid obesity,” The New England Journal of Medicine, vol. 333, no. 6, pp. 352–354, 1995. View at Publisher · View at Google Scholar · View at PubMed
  84. N. Sakane, T. Yoshida, T. Umekawa, A. Kogure, Y. Takakura, and M. Kondo, “Effects of Trp64Arg mutation in the β3-adrenergic receptor gene on weight loss, body fat distribution, glycemic control, and insulin resistance in obese type 2 diabetic patients,” Diabetes Care, vol. 20, no. 12, pp. 1887–1890, 1997. View at Google Scholar
  85. T. Umekawa, T. Yoshida, N. Sakane, A. Kogure, M. Kondo, and H. Honjyo, “Trp64Arg mutation of β3-adrenoceptor gene deteriorates lipolysis induced by β3-adrenoceptor agonist in human omental adipocytes,” Diabetes, vol. 48, no. 1, pp. 117–120, 1999. View at Publisher · View at Google Scholar
  86. K. Endo, H. Yanagi, C. Hirano, H. Hamaguchi, S. Tsuchiya, and S. Tomura, “Association of Trp64Arg polymorphism of the β3-adrenergic receptor gene and no association of Gln223Arg polymorphism of the leptin receptor gene in Japanese schoolchildren with obesity,” International Journal of Obesity, vol. 24, no. 4, pp. 443–449, 2000. View at Google Scholar
  87. T. Oizumi, M. Daimon, T. Saitoh et al., “Genotype Arg/Arg, but not Trp/Arg, of the Trp64Arg polymorphism of the β3-adrenergic receptor is associated with type 2 diabetes and obesity in a large Japanese sample,” Diabetes Care, vol. 24, no. 9, pp. 1579–1583, 2001. View at Google Scholar · View at Scopus
  88. A. P. Gjesing, G. Andersen, K. S. Burgdorf et al., “Studies of the associations between functional β2-adrenergic receptor variants and obesity, hypertension and type 2 diabetes in 7,808 white subjects,” Diabetologia, vol. 50, no. 3, pp. 563–568, 2007. View at Publisher · View at Google Scholar · View at PubMed
  89. N. Kurokawa, K. Nakai, S. Kameo, Z. M. Liu, and H. Satoh, “Association of BMI with the β3-adrenergic receptor gene polymorphism in Japanese: meta-analysis,” Obesity Research, vol. 9, no. 12, pp. 741–745, 2001. View at Google Scholar
  90. P. Arner, “The β3-adrenergic receptor—a cause and cure of obesity?” The New England Journal of Medicine, vol. 333, no. 6, pp. 382–383, 1995. View at Publisher · View at Google Scholar · View at PubMed
  91. J. Hoffstedt, O. Poirier, A. Thörne et al., “Polymorphism of the human β3-adrenoceptor gene forms a well-conserved haplotype that is associated with moderate obesity and altered receptor function,” Diabetes, vol. 48, no. 1, pp. 203–205, 1999. View at Publisher · View at Google Scholar
  92. J. Walston, K. Silver, C. Bogardus et al., “Time of onset of non-insulin-dependent diabetes mellitus and genetic variation in the β3-adrenergic-receptor gene,” The New England Journal of Medicine, vol. 333, no. 6, pp. 343–347, 1995. View at Publisher · View at Google Scholar · View at PubMed
  93. D. L. Ellsworth, S. A. Coady, W. Chen, S. R. Srinivasan, E. Boerwinkle, and G. S. Berenson, “Interactive effects between polymorphisms in the β-adrenergic receptors and longitudinal changes in obesity,” Obesity Research, vol. 13, no. 3, pp. 519–526, 2005. View at Google Scholar
  94. I. C. Trombetta, L. T. Batalha, M. U. P. B. Rondon et al., “Gly16+Glu27 β2-adrenoceptor polymorphisms cause increased forearm blood flow responses to mental stress and handgrip in humans,” Journal of Applied Physiology, vol. 98, no. 3, pp. 787–794, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  95. A. Sandilands, G. Yeo, M. J. Brown, and K. M. O'Shaughnessy, “Functional responses of human β1 adrenoceptors with defined haplotypes for the common 389R>G and 49S>G polymorphisms,” Pharmacogenetics, vol. 14, no. 6, pp. 343–349, 2004. View at Publisher · View at Google Scholar · View at Scopus
  96. M. Tomaszewski, N. J. R. Brain, F. J. Charchar et al., “Essential hypertension and β2-adrenergic receptor gene: linkage and association analysis,” Hypertension, vol. 40, no. 3, pp. 286–291, 2002. View at Publisher · View at Google Scholar · View at Scopus
  97. S. M. Herrmann, V. Nicaud, L. Tiret et al., “Polymorphisms of the β2-adrenoceptor (ADRB2) gene and essential hypertension: the ECTIM and PEGASE studies,” Journal of Hypertension, vol. 20, no. 2, pp. 229–235, 2002. View at Publisher · View at Google Scholar · View at Scopus
  98. K. Masuo, H. Mikami, T. Ogihara, and M. L. Tuck, “Sympathetic nerve hyperactivity precedes hyperinsulinemia and blood pressure elevation in a young, nonobese Japanese population,” American Journal of Hypertension, vol. 10, no. 1, pp. 77–83, 1997. View at Publisher · View at Google Scholar · View at Scopus
  99. W. B. Kannel and D. L. McGee, “Diabetes and cardiovascular disease. The Framingham study,” The Journal of the American Medical Association, vol. 241, no. 19, pp. 2035–2038, 1979. View at Publisher · View at Google Scholar · View at Scopus
  100. V. Frighi, I. Stratton, R. Holman, D. Matthews, A. Neil, and R. Turner, “Hypertension in Diabetes Study (HDS): II. Increased risk of cardiovascular complications in hypertensive type 2 diabetic patients,” Journal of Hypertension, vol. 11, no. 3, pp. 319–325, 1993. View at Google Scholar · View at Scopus
  101. G. J. J. Tack, P. Smits, J. J. Willemsen, J. W. M. Lenders, T. Thien, and J. A. Lutterman, “Effects of insulin on vascular tone and sympathetic nervous system in NIDDM,” Diabetes, vol. 45, no. 1, pp. 15–22, 1996. View at Google Scholar · View at Scopus
  102. K. Masuo, H. Rakugi, T. Ogihara, M. D. Esler, and G. W. Lambert, “Cardiovascular and renal complications of type 2 diabetes in obesity: role of sympathetic nerve activity and insulin resistance,” Current Diabetes Reviews, vol. 6, no. 2, pp. 58–67, 2010. View at Publisher · View at Google Scholar · View at Scopus
  103. S. Julius and S. Nesbitt, “Sympathetic overactivity in hypertension a moving target,” American Journal of Hypertension, vol. 9, no. 11, pp. 113s–120s, 1996. View at Google Scholar · View at Scopus
  104. G. Mancia, G. Grassi, C. Giannattasio, and G. Seravalle, “Sympathetic activation in the pathogenesis of hypertension and progression of organ damage,” Hypertension, vol. 34, no. 4, part 2, pp. 724–728, 1999. View at Google Scholar · View at Scopus
  105. M. Esler, G. Jennings, and G. Lambert, “Noradrenaline release and the pathophysiology of primary human hypertension,” American Journal of Hypertension, vol. 2, no. 3, part 2, pp. 140S–146S, 1989. View at Google Scholar
  106. J. A. Joles and H. A. Koomans, “Causes and consequences of increased sympathetic activity in renal disease,” Hypertension, vol. 43, no. 4, pp. 699–706, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  107. M. P. Schlaich, F. Socratous, S. Hennebry et al., “Sympathetic activation in chronic renal failure,” Journal of the American Society of Nephrology, vol. 20, no. 5, pp. 933–939, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  108. R. E. Bulger, T. J. Burke, and R. E. Cronin, “Morphology of norepinephrine-induced acute renal failure in the dog,” Anatomical Record, vol. 214, no. 4, pp. 341–347, 1986. View at Google Scholar
  109. K. Amann, A. Koch, J. Hofstetter et al., “Glomerulosclerosis and progression: effect of subantihypertensive doses of α and β blockers,” Kidney International, vol. 60, no. 4, pp. 1309–1323, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  110. C. Zoccali, F. Mallamaci, S. Parlongo et al., “Plasma norepinephrine predicts survival and incident cardiovascular events in patients with end-stage renal disease,” Circulation, vol. 105, no. 11, pp. 1354–1359, 2002. View at Publisher · View at Google Scholar · View at Scopus
  111. M. Petersson, P. Friberg, G. Eisenhofer, G. Lambert, and B. Rundqvist, “Long-term outcome in relation to renal sympathetic activity in patients with chronic heart failure,” European Heart Journal, vol. 26, no. 9, pp. 906–913, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  112. K. Masuo, T. Katsuya, K. Sugimoto et al., “High plasma norepinephrine levels associated with β2-adrenoceptor polymorphisms predict future renal damage in nonobese normotensive individuals,” Hypertension Research, vol. 30, no. 6, pp. 503–511, 2007. View at Publisher · View at Google Scholar · View at PubMed
  113. A. Ksiazek and W. Załuska, “Sympathetic overactivity in uremia,” Journal of Renal Nutrition, vol. 18, no. 1, pp. 118–121, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  114. H. Krum, M. Schlaich, R. Whitbourn et al., “Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study,” The Lancet, vol. 373, no. 9671, pp. 1275–1281, 2009. View at Publisher · View at Google Scholar · View at Scopus
  115. M. P. Schlaich, P. A. Sobotka, H. Krum, E. Lambert, and M. D. Esler, “Renal sympathetic-nerve ablation for uncontrolled hypertension,” The New England Journal of Medicine, vol. 361, no. 9, pp. 932–934, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus