{beta}-Adrenoceptor gene variation and intermediate physiological traits: prediction of distant phenotype.
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.
Eisenach
John H
JH
Departments of Anesthesiology, Mayo Clinic, Rochester, MN 55905, USA. eisenach.john@mayo.edu
Wittwer
Erica D
ED
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*
C547787:ADRB1 protein, human; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D022702:Receptors, Adrenergic, beta-3
Gynecol Endocrinol. 2008 Mar;24(3):133-8
18335327
J Appl Physiol (1985). 2005 Nov;99(5):1776-81
15994241
J Am Coll Cardiol. 2005 Dec 6;46(11):2111-5
16325050
Mol Genet Metab. 2008 May;94(1):90-7
18249022
Obes Res. 2005 Mar;13(3):519-26
15833937
Zhonghua Nei Ke Za Zhi. 2008 Oct;47(10):811-4
19080138
Br J Pharmacol. 2001 Jul;133(5):708-12
11429395
Heart Rhythm. 2008 May;5(5):694-700
18452871
Int J Obes (Lond). 2005 May;29(5):458-62
15685248
Ann Nutr Metab. 2008;52(4):267-71
18617734
Am J Hypertens. 2003 Nov;16(11 Pt 1):945-51
14573333
Pharmacogenet Genomics. 2005 May;15(5):267-75
15864127
Int J Obes (Lond). 2007 May;31(5):813-9
17130852
Pharmacogenetics. 2004 Nov;14(11):711-6
15564877
Am J Hum Genet. 2002 Apr;70(4):935-42
11854867
Proc Natl Acad Sci U S A. 2000 Sep 12;97(19):10483-8
10984540
Med Sci Monit. 2007 May;13(5):BR112-8
17476189
BMJ. 2009 Feb 03;338:b219
19193613
J Appl Physiol (1985). 2005 Mar;98(3):787-94
15703163
Circulation. 1999 May 4;99(17):2251-4
10226089
Biochemistry. 1994 Aug 16;33(32):9414-9
7915137
Ann Clin Biochem. 2008 May;45(Pt 3):313-5
18482921
J Physiol. 2006 Aug 1;574(Pt 3):955-65
16740612
J Physiol. 2006 Feb 15;571(Pt 1):121-30
16339181
Exp Diabetes Res. 2009;2009:605139
20069060
Diabetes. 1999 Jan;48(1):117-20
9892231
J Allergy Clin Immunol. 2006 Jan;117(1):18-24; quiz 25
16387578
Am Heart J. 2000 Mar;139(3):537-42
10689270
Clin Pharmacol Ther. 2005 Sep;78(3):232-8
16153394
N Engl J Med. 2001 Oct 4;345(14):1030-5
11586955
Am J Respir Crit Care Med. 2006 Nov 15;174(10):1101-9
16931635
Circulation. 2001 Feb 27;103(8):1048-50
11222464
Pharmacogenetics. 2004 Aug;14(8):517-22
15284533
N Engl J Med. 2002 Feb 14;346(7):536-8
11844862
Hypertension. 2000 Sep;36(3):371-5
10988267
Clin Sci (Lond). 2003 May;104(5):509-20
12519093
J Physiol. 2003 Jan 15;546(Pt 2):583-9
12527744
Hypertension. 1999 Jun;33(6):1425-30
10373227
Pharmacogenetics. 2003 Feb;13(2):59-66
12563174
Br J Pharmacol. 2009 Jan;156(1):127-34
19133996
J Biol Chem. 1993 Nov 5;268(31):23116-21
7901205
Med Sci Sports Exerc. 2006 May;38(5):882-6
16672841
Drugs. 2007;67 Suppl 2:3-13
17999559
Metabolism. 2007 Jun;56(6):757-65
17512307
Am J Respir Cell Mol Biol. 1995 Jul;13(1):25-33
7598936
Int J Obes Relat Metab Disord. 2004 Feb;28(2):185-90
14610528
Physiol Genomics. 2004 Feb 13;16(3):323-8
14665698
Int J Obes (Lond). 2008 Aug;32(8):1240-9
18574485
Proc Natl Acad Sci U S A. 2006 Jul 25;103(30):11288-93
16844790
Pharmacol Ther. 2008 Jan;117(1):1-29
17916379
J Appl Physiol (1985). 2002 May;92(5):2019-25
11960953