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Gene Review

ADRB2  -  adrenoceptor beta 2, surface

Homo sapiens

Synonyms: ADRB2R, ADRBR, B2AR, BAR, BETA2AR, ...
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Disease relevance of ADRB2

  • CONCLUSIONS : From our present analysis we conclude that the ADRB2 gene polymorphisms studied do not contribute in any important way to the risk of essential hypertension or MI in subjects of European ancestry [1].
  • We investigated whether genetic variation of the ADRB2 gene might be related to essential hypertension or myocardial infarction (MI) [1].
  • CONCLUSIONS: Variants of the ADRB2, ADRA1d and IL-4 genes may be related to a predisposition to interstitial cystitis [2].
  • OBJECTIVE: To assess the effects of a polymorphism in codon 16 (Arg16-->Gly) of the ADRB2 gene, which has been associated with a decrease in beta2-receptor density and efficiency, on longitudinal changes in obesity from childhood to young adulthood in a biracial cohort [3].
  • CONCLUSION: Only variations in the ADRB2 gene and LEPR gene, may contribute to susceptibility to weight gain [4].

Psychiatry related information on ADRB2


High impact information on ADRB2


Chemical compound and disease context of ADRB2


Biological context of ADRB2

  • The beta(2)AR genotypes at codons 16 and 27 of ADRB2 were determined [18].
  • OBJECTIVES: Our aim was to measure bronchodilator response in patients with asthma stratified by ADRB2 haplotype [19].
  • CONCLUSIONS: Genetic variation of the ADRB2 does not influence the immediate response to inhaled beta2-agonist [19].
  • Polymorphisms of the ADRB2 gene have been shown to be potentially related to essential hypertension and other non-cardiovascular disease phenotypes [1].
  • At bp 46 in ADRB2, GG homozygotes had higher resting DBP than subjects possessing any A allele (P < 0.05) [20].

Anatomical context of ADRB2


Associations of ADRB2 with chemical compounds

  • These effects are mediated primarily through activation of the tumor cell cyclic AMP (cAMP)-protein kinase A (PKA) signaling pathway by the beta(2) adrenergic receptor (encoded by ADRB2) [25].
  • CONCLUSION: Our family-based study provided the first evidence that ADRB2 R16G polymorphism may play an important role in DBP response to benazepril treatment, although the magnitude of the effect appears to be modified by other risk factors such as plasma lipid and glucose profiles [13].
  • The ADRB2 Glu27Glu subjects had lower plasma glycerol levels (P = 0.026), while plasma triglycerides (P <0.001) and the insulin:glucose ratio were higher (P = 0.046) as compared to the Gln27Gln group along the peak oxygen consumption trial intervention [26].
  • Concentration-response curves to (-)-epinephrine were constructed in the presence and absence of selective antagonists for beta 1 AR (CGP 20712A) and beta 2 AR (ICI 118,551) [23].
  • For the beta 2AR, this cysteine has been shown to be important for stimulatory G protein (Gs) coupling and agonist-promoted desensitization [27].

Physical interactions of ADRB2


Enzymatic interactions of ADRB2


Regulatory relationships of ADRB2


Other interactions of ADRB2


Analytical, diagnostic and therapeutic context of ADRB2

  • METHODS : Four ADRB2 gene polymorphisms C19R (T-47C), T-20C, G16R (G+46A), Q27E (C+79G) were investigated in two studies: PEGASE, a study of moderate to severe hypertension (707 cases) conducted in France, and ECTIM, a case-control study of MI (1178 cases, 1187 controls) conducted in France, Northern Ireland and Scotland [1].
  • RESULTS: The distribution of the genotype frequencies of ADRB2 + 79 C/G was significantly different between the COPD and the control groups in the Egyptians (p = 0.002) [44].
  • In conclusion, ADRB2 Arg16Gln27 haplotype may significantly increase the risk of adverse outcomes in patients with HF receiving contemporary HF pharmacotherapy [45].
  • ADRB2 polymorphisms and asthma susceptibility: transmission disequilibrium test and meta-analysis [46].
  • Polymorphisms in the ADRB2 gene have been associated with obesity and various weight-related traits in cross-sectional studies of adults, but little is known about the effects of the ADRB2 gene on childhood obesity or the propensity to gain weight over time [3].


  1. Polymorphisms of the beta2 -adrenoceptor (ADRB2) gene and essential hypertension: the ECTIM and PEGASE studies. Herrmann, S.M., Nicaud, V., Tiret, L., Evans, A., Kee, F., Ruidavets, J.B., Arveiler, D., Luc, G., Morrison, C., Hoehe, M.R., Paul, M., Cambien, F. J. Hypertens. (2002) [Pubmed]
  2. Molecular analysis of adrenergic receptor genes and interleukin-4/interleukin-4 receptor genes in patients with interstitial cystitis. Sugaya, K., Nishijima, S., Yamada, T., Miyazato, M., Hatano, T., Ogawa, Y. J. Urol. (2002) [Pubmed]
  3. Influence of the beta2-adrenergic receptor Arg16Gly polymorphism on longitudinal changes in obesity from childhood through young adulthood in a biracial cohort: the Bogalusa Heart Study. Ellsworth, D.L., Coady, S.A., Chen, W., Srinivasan, S.R., Elkasabany, A., Gustat, J., Boerwinkle, E., Berenson, G.S. Int. J. Obes. Relat. Metab. Disord. (2002) [Pubmed]
  4. Genetic factors as predictors of weight gain in young adult Dutch men and women. van Rossum, C.T., Hoebee, B., Seidell, J.C., Bouchard, C., van Baak, M.A., de Groot, C.P., Chagnon, M., de Graaf, C., Saris, W.H. Int. J. Obes. Relat. Metab. Disord. (2002) [Pubmed]
  5. The 27Glu polymorphism of the beta2-adrenergic receptor gene interacts with physical activity influencing obesity risk among female subjects. Corbalán, M.S., Marti, A., Forga, L., Martínez-González, M.A., Martínez, J.A. Clin. Genet. (2002) [Pubmed]
  6. Three major haplotypes of the beta2 adrenergic receptor define psychological profile, blood pressure, and the risk for development of a common musculoskeletal pain disorder. Diatchenko, L., Anderson, A.D., Slade, G.D., Fillingim, R.B., Shabalina, S.A., Higgins, T.J., Sama, S., Belfer, I., Goldman, D., Max, M.B., Weir, B.S., Maixner, W. Am. J. Med. Genet. B Neuropsychiatr. Genet. (2006) [Pubmed]
  7. Neutrophil beta2-adrenergic receptor coupling efficiency to Gs protein in subjects with post-traumatic stress disorder and normal controls. Gurguis, G.N., Andrews, R., Antai-Otong, D., Vo, S.P., Blakeley, J.E., Orsulak, P.J., Rush, A.J. Psychopharmacology (Berl.) (1999) [Pubmed]
  8. Adrenergic receptor function in panic disorder. II. Neutrophil beta 2 receptors: Gs protein coupling, effects of imipramine treatment and relationship to treatment outcome. Gurguis, G.N., Blakeley, J.E., Antai-Otong, D., Vo, S.P., Orsulak, P.J., Petty, F., Rush, A.J. Journal of psychiatric research. (1999) [Pubmed]
  9. Adrenergic receptors in premenstrual dysphoric disorder. II. Neutrophil beta2-adrenergic receptors: Gs protein coupling, phase of menstrual cycle and prediction of luteal phase symptom severity. Gurguis, G.N., Yonkers, K.A., Blakeley, J.E., Phan, S.P., Williams, A., Rush, A.J. Psychiatry research. (1998) [Pubmed]
  10. The effect of common polymorphisms of the beta2-adrenergic receptor on agonist-mediated vascular desensitization. Dishy, V., Sofowora, G.G., Xie, H.G., Kim, R.B., Byrne, D.W., Stein, C.M., Wood, A.J. N. Engl. J. Med. (2001) [Pubmed]
  11. A comparison of beclomethasone, salmeterol, and placebo in children with asthma. Canadian Beclomethasone Dipropionate-Salmeterol Xinafoate Study Group. Simons, F.E. N. Engl. J. Med. (1997) [Pubmed]
  12. Identification of a Gs activator region of the beta 2-adrenergic receptor that is autoregulated via protein kinase A-dependent phosphorylation. Okamoto, T., Murayama, Y., Hayashi, Y., Inagaki, M., Ogata, E., Nishimoto, I. Cell (1991) [Pubmed]
  13. Beta2 adrenergic receptor gene Arg16Gly polymorphism is associated with therapeutic efficacy of benazepril on essential hypertension in Chinese. Huang, G., Xing, H., Hao, K., Peng, S., Wu, D., Guang, W., Huang, A., Hong, X., Wang, Y., Feng, Y., Zhang, Y., Li, J., Chen, C., Wang, B., Zhang, X., Li, D., Yu, Y., Liu, J., Zhu, G., Huo, Y., Chen, D., Hou, Y., Wang, X., Xu, X., Niu, T., Xu, X. Clin. Exp. Hypertens. (2004) [Pubmed]
  14. Inhibition of beta-adrenergic receptor kinase prevents rapid homologous desensitization of beta 2-adrenergic receptors. Lohse, M.J., Lefkowitz, R.J., Caron, M.G., Benovic, J.L. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  15. Metabolic and calorigenic effects of dopexamine in healthy volunteers. Geisser, W., Träger, K., Hähn, A., Georgieff, M., Ensinger, H. Crit. Care Med. (1997) [Pubmed]
  16. Beta2-adrenoceptor polymorphisms relate to insulin resistance and sympathetic overactivity as early markers of metabolic disease in nonobese, normotensive individuals. Masuo, K., Katsuya, T., Fu, Y., Rakugi, H., Ogihara, T., Tuck, M.L. Am. J. Hypertens. (2005) [Pubmed]
  17. Disodium cromoglycate does not prevent terbutaline-induced desensitization of beta 2-adrenoceptor-mediated cardiovascular in vivo functions in human volunteers. Schäfers, R.F., Piest, U., von Birgelen, C., Jakubetz, J., Daul, A.E., Philipp, T., Brodde, O.E. J. Cardiovasc. Pharmacol. (1999) [Pubmed]
  18. Arg16 homozygosity of the beta2-adrenergic receptor improves the outcome after beta2-agonist tocolysis for preterm labor. Landau, R., Morales, M.A., Antonarakis, S.E., Blouin, J.L., Smiley, R.M. Clin. Pharmacol. Ther. (2005) [Pubmed]
  19. Bronchodilator response in relation to beta2-adrenoceptor haplotype in patients with asthma. Taylor, D.R., Epton, M.J., Kennedy, M.A., Smith, A.D., Iles, S., Miller, A.L., Littlejohn, M.D., Cowan, J.O., Hewitt, T., Swanney, M.P., Brassett, K.P., Herbison, G.P. Am. J. Respir. Crit. Care Med. (2005) [Pubmed]
  20. Variability within alpha- and beta-adrenoreceptor genes as a predictor of cardiovascular function at rest and in response to mental challenge. McCaffery, J.M., Pogue-Geile, M.F., Ferrell, R.E., Petro, N., Manuck, S.B. J. Hypertens. (2002) [Pubmed]
  21. Polymorphism of beta-adrenergic receptors and susceptibility to open-angle glaucoma. Inagaki, Y., Mashima, Y., Fuse, N., Funayama, T., Ohtake, Y., Yasuda, N., Murakami, A., Hotta, Y., Fukuchi, T., Tsubota, K. Mol. Vis. (2006) [Pubmed]
  22. A kinase-regulated PDZ-domain interaction controls endocytic sorting of the beta2-adrenergic receptor. Cao, T.T., Deacon, H.W., Reczek, D., Bretscher, A., von Zastrow, M. Nature (1999) [Pubmed]
  23. Coexistence of functioning beta 1- and beta 2-adrenoceptors in single myocytes from human ventricle. del Monte, F., Kaumann, A.J., Poole-Wilson, P.A., Wynne, D.G., Pepper, J., Harding, S.E. Circulation (1993) [Pubmed]
  24. Molecular determinants underlying the formation of stable intracellular G protein-coupled receptor-beta-arrestin complexes after receptor endocytosis*. Oakley, R.H., Laporte, S.A., Holt, J.A., Barak, L.S., Caron, M.G. J. Biol. Chem. (2001) [Pubmed]
  25. Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma. Thaker, P.H., Han, L.Y., Kamat, A.A., Arevalo, J.M., Takahashi, R., Lu, C., Jennings, N.B., Armaiz-Pena, G., Bankson, J.A., Ravoori, M., Merritt, W.M., Lin, Y.G., Mangala, L.S., Kim, T.J., Coleman, R.L., Landen, C.N., Li, Y., Felix, E., Sanguino, A.M., Newman, R.A., Lloyd, M., Gershenson, D.M., Kundra, V., Lopez-Berestein, G., Lutgendorf, S.K., Cole, S.W., Sood, A.K. Nat. Med. (2006) [Pubmed]
  26. Basal fat oxidation and after a peak oxygen consumption test in obese women with a beta2 adrenoceptor gene polymorphism. Macho-Azcarate, T., Marti, A., Calabuig, J., Martinez, J.A. J. Nutr. Biochem. (2003) [Pubmed]
  27. The palmitoylated cysteine of the cytoplasmic tail of alpha 2A-adrenergic receptors confers subtype-specific agonist-promoted downregulation. Eason, M.G., Jacinto, M.T., Theiss, C.T., Liggett, S.B. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  28. A C-terminal motif found in the beta2-adrenergic receptor, P2Y1 receptor and cystic fibrosis transmembrane conductance regulator determines binding to the Na+/H+ exchanger regulatory factor family of PDZ proteins. Hall, R.A., Ostedgaard, L.S., Premont, R.T., Blitzer, J.T., Rahman, N., Welsh, M.J., Lefkowitz, R.J. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  29. c-Src tyrosine kinase binds the beta 2-adrenergic receptor via phospho-Tyr-350, phosphorylates G-protein-linked receptor kinase 2, and mediates agonist-induced receptor desensitization. Fan , G., Shumay, E., Malbon, C.C., Wang , H. J. Biol. Chem. (2001) [Pubmed]
  30. Iodinated analogs of trimetoquinol as highly potent and selective beta 2-adrenoceptor ligands. De Los Angeles, J.E., Nikulin, V.I., Shams, G., Konkar, A.A., Mehta, R., Feller, D.R., Miller, D.D. J. Med. Chem. (1996) [Pubmed]
  31. Protein kinase A regulates AKAP250 (gravin) scaffold binding to the beta2-adrenergic receptor. Tao, J., Wang, H.Y., Malbon, C.C. EMBO J. (2003) [Pubmed]
  32. Members of the G protein-coupled receptor kinase family that phosphorylate the beta2-adrenergic receptor facilitate sequestration. Ménard, L., Ferguson, S.S., Barak, L.S., Bertrand, L., Premont, R.T., Colapietro, A.M., Lefkowitz, R.J., Caron, M.G. Biochemistry (1996) [Pubmed]
  33. The beta-adrenergic receptor is a substrate for the insulin receptor tyrosine kinase. Baltensperger, K., Karoor, V., Paul, H., Ruoho, A., Czech, M.P., Malbon, C.C. J. Biol. Chem. (1996) [Pubmed]
  34. The beta-adrenergic receptor kinase (GRK2) is regulated by phospholipids. Onorato, J.J., Gillis, M.E., Liu, Y., Benovic, J.L., Ruoho, A.E. J. Biol. Chem. (1995) [Pubmed]
  35. RNA silencing identifies PDE4D5 as the functionally relevant cAMP phosphodiesterase interacting with beta arrestin to control the protein kinase A/AKAP79-mediated switching of the beta2-adrenergic receptor to activation of ERK in HEK293B2 cells. Lynch, M.J., Baillie, G.S., Mohamed, A., Li, X., Maisonneuve, C., Klussmann, E., van Heeke, G., Houslay, M.D. J. Biol. Chem. (2005) [Pubmed]
  36. Beta 2-adrenergic receptor agonist induces IL-18 production without IL-12 production. Takahashi, H.K., Iwagaki, H., Mori, S., Yoshino, T., Tanaka, N., Nishibori, M. J. Neuroimmunol. (2004) [Pubmed]
  37. Selective regulation of beta 2-adrenergic receptor gene expression by interleukin-1 in cultured human lung tumor cells. Szentendrei, T., Lazar-Wesley, E., Nakane, T., Virmani, M., Kunos, G. J. Cell. Physiol. (1992) [Pubmed]
  38. beta2-Adrenergic receptor regulation by GIT1, a G protein-coupled receptor kinase-associated ADP ribosylation factor GTPase-activating protein. Premont, R.T., Claing, A., Vitale, N., Freeman, J.L., Pitcher, J.A., Patton, W.A., Moss, J., Vaughan, M., Lefkowitz, R.J. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  39. A proline-rich region of the third intracellular loop imparts phenotypic beta 1-versus beta 2-adrenergic receptor coupling and sequestration. Green, S.A., Liggett, S.B. J. Biol. Chem. (1994) [Pubmed]
  40. Cloning of the cDNA for the human beta 1-adrenergic receptor. Frielle, T., Collins, S., Daniel, K.W., Caron, M.G., Lefkowitz, R.J., Kobilka, B.K. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  41. Molecular cloning and expression of GRK6. A new member of the G protein-coupled receptor kinase family. Benovic, J.L., Gomez, J. J. Biol. Chem. (1993) [Pubmed]
  42. Identification of the G protein-coupled receptor kinase phosphorylation sites in the human beta2-adrenergic receptor. Fredericks, Z.L., Pitcher, J.A., Lefkowitz, R.J. J. Biol. Chem. (1996) [Pubmed]
  43. Lack of beta 3-adrenergic receptor mRNA expression in adipose and other metabolic tissues in the adult human. Thomas, R.F., Liggett, S.B. Mol. Pharmacol. (1993) [Pubmed]
  44. Polymorphisms of IL4, IL13, and ADRB2 genes in COPD. Hegab, A.E., Sakamoto, T., Saitoh, W., Massoud, H.H., Massoud, H.M., Hassanein, K.M., Sekizawa, K. Chest (2004) [Pubmed]
  45. Relation of beta(2)-Adrenoceptor Haplotype to Risk of Death and Heart Transplantation in Patients With Heart Failure. Shin, J., Lobmeyer, M.T., Gong, Y., Zineh, I., Langaee, T.Y., Yarandi, H., Schofield, R.S., Aranda, J.M., Hill, J.A., Pauly, D.F., Johnson, J.A. Am. J. Cardiol. (2007) [Pubmed]
  46. ADRB2 polymorphisms and asthma susceptibility: transmission disequilibrium test and meta-analysis. Migita, O., Noguchi, E., Jian, Z., Shibasaki, M., Migita, T., Ichikawa, K., Matsui, A., Arinami, T. Int. Arch. Allergy Immunol. (2004) [Pubmed]
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