title: {beta}-Adrenoceptor gene variation and intermediate physiological traits: prediction of distant phenotype.
abstract: Intermediate physiological phenotype is the genetic and environmental influence on functional physiological characteristics with direct prognostic relevance to distant, more complex phenotypes, such as cardiovascular and metabolic disease. Increasingly available and affordable genotyping techniques have created an explosion of information on candidate gene variation and its relationship to intermediate physiological traits. Variation in beta-adrenoceptor genes is an intense focus of investigation because beta-adrenoceptors are: (1) ubiquitous in organ system distribution; (2) integral to a multitude of physiological processes; (3) well described in cardiovascular and metabolic disease; and (4) major pharmacological treatment targets. Furthermore, knowledge of functional gene variants in these receptors predates the description of the human genome. This review highlights the influence of common gene variation in the three beta-adrenoceptor subtypes on intermediate physiological phenotype predictive of cardiovascular disease and obesity. Although further information is needed to replicate this information across populations, this review condenses and summarizes growing trends in specific pleiotropic effects of beta-adrenoceptor polymorphisms and suggests which variants may be predictive of distant phenotype.
authors.affiliation: Departments of Anesthesiology, Mayo Clinic, Rochester, MN 55905, USA. eisenach.john@mayo.edu
authors.forename: John H
authors.initials: JH
authors.lastname: Eisenach
authors.forename: Erica D
authors.initials: ED
authors.lastname: Wittwer
mesh_terms: D000595:Amino Acid Sequence; D002318:Cardiovascular Diseases / Q000235:genetics*; D003920:Diabetes Mellitus / Q000235:genetics; D005260:Female; D006339:Heart Rate / Q000235:genetics; D006801:Humans; D006973:Hypertension / Q000235:genetics; D007333:Insulin Resistance / Q000235:genetics; D008066:Lipolysis / Q000235:genetics; D008297:Male; D009765:Obesity / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics*
chemical_list: C547787:ADRB1 protein, human; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D022702:Receptors, Adrenergic, beta-3
references.citation: Gynecol Endocrinol. 2008 Mar;24(3):133-8
references.pmid: 18335327
references.citation: J Appl Physiol (1985). 2005 Nov;99(5):1776-81
references.pmid: 15994241
references.citation: J Am Coll Cardiol. 2005 Dec 6;46(11):2111-5
references.pmid: 16325050
references.citation: Mol Genet Metab. 2008 May;94(1):90-7
references.pmid: 18249022
references.citation: Obes Res. 2005 Mar;13(3):519-26
references.pmid: 15833937
references.citation: Zhonghua Nei Ke Za Zhi. 2008 Oct;47(10):811-4
references.pmid: 19080138
references.citation: Br J Pharmacol. 2001 Jul;133(5):708-12
references.pmid: 11429395
references.citation: Heart Rhythm. 2008 May;5(5):694-700
references.pmid: 18452871
references.citation: Int J Obes (Lond). 2005 May;29(5):458-62
references.pmid: 15685248
references.citation: Ann Nutr Metab. 2008;52(4):267-71
references.pmid: 18617734
references.citation: Am J Hypertens. 2003 Nov;16(11 Pt 1):945-51
references.pmid: 14573333
references.citation: Pharmacogenet Genomics. 2005 May;15(5):267-75
references.pmid: 15864127
references.citation: Int J Obes (Lond). 2007 May;31(5):813-9
references.pmid: 17130852
references.citation: Pharmacogenetics. 2004 Nov;14(11):711-6
references.pmid: 15564877
references.citation: Am J Hum Genet. 2002 Apr;70(4):935-42
references.pmid: 11854867
references.citation: Proc Natl Acad Sci U S A. 2000 Sep 12;97(19):10483-8
references.pmid: 10984540
references.citation: Med Sci Monit. 2007 May;13(5):BR112-8
references.pmid: 17476189
references.citation: BMJ. 2009 Feb 03;338:b219
references.pmid: 19193613
references.citation: J Appl Physiol (1985). 2005 Mar;98(3):787-94
references.pmid: 15703163
references.citation: Circulation. 1999 May 4;99(17):2251-4
references.pmid: 10226089
references.citation: Biochemistry. 1994 Aug 16;33(32):9414-9
references.pmid: 7915137
references.citation: Ann Clin Biochem. 2008 May;45(Pt 3):313-5
references.pmid: 18482921
references.citation: J Physiol. 2006 Aug 1;574(Pt 3):955-65
references.pmid: 16740612
references.citation: J Physiol. 2006 Feb 15;571(Pt 1):121-30
references.pmid: 16339181
references.citation: Exp Diabetes Res. 2009;2009:605139
references.pmid: 20069060
references.citation: Diabetes. 1999 Jan;48(1):117-20
references.pmid: 9892231
references.citation: J Allergy Clin Immunol. 2006 Jan;117(1):18-24; quiz 25
references.pmid: 16387578
references.citation: Am Heart J. 2000 Mar;139(3):537-42
references.pmid: 10689270
references.citation: Clin Pharmacol Ther. 2005 Sep;78(3):232-8
references.pmid: 16153394
references.citation: N Engl J Med. 2001 Oct 4;345(14):1030-5
references.pmid: 11586955
references.citation: Am J Respir Crit Care Med. 2006 Nov 15;174(10):1101-9
references.pmid: 16931635
references.citation: Circulation. 2001 Feb 27;103(8):1048-50
references.pmid: 11222464
references.citation: Pharmacogenetics. 2004 Aug;14(8):517-22
references.pmid: 15284533
references.citation: N Engl J Med. 2002 Feb 14;346(7):536-8
references.pmid: 11844862
references.citation: Hypertension. 2000 Sep;36(3):371-5
references.pmid: 10988267
references.citation: Clin Sci (Lond). 2003 May;104(5):509-20
references.pmid: 12519093
references.citation: J Physiol. 2003 Jan 15;546(Pt 2):583-9
references.pmid: 12527744
references.citation: Hypertension. 1999 Jun;33(6):1425-30
references.pmid: 10373227
references.citation: Pharmacogenetics. 2003 Feb;13(2):59-66
references.pmid: 12563174
references.citation: Br J Pharmacol. 2009 Jan;156(1):127-34
references.pmid: 19133996
references.citation: J Biol Chem. 1993 Nov 5;268(31):23116-21
references.pmid: 7901205
references.citation: Med Sci Sports Exerc. 2006 May;38(5):882-6
references.pmid: 16672841
references.citation: Drugs. 2007;67 Suppl 2:3-13
references.pmid: 17999559
references.citation: Metabolism. 2007 Jun;56(6):757-65
references.pmid: 17512307
references.citation: Am J Respir Cell Mol Biol. 1995 Jul;13(1):25-33
references.pmid: 7598936
references.citation: Int J Obes Relat Metab Disord. 2004 Feb;28(2):185-90
references.pmid: 14610528
references.citation: Physiol Genomics. 2004 Feb 13;16(3):323-8
references.pmid: 14665698
references.citation: Int J Obes (Lond). 2008 Aug;32(8):1240-9
references.pmid: 18574485
references.citation: Proc Natl Acad Sci U S A. 2006 Jul 25;103(30):11288-93
references.pmid: 16844790
references.citation: Pharmacol Ther. 2008 Jan;117(1):1-29
references.pmid: 17916379
references.citation: J Appl Physiol (1985). 2002 May;92(5):2019-25
references.pmid: 11960953