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beta(2)-Adrenergic receptor polymorphisms and determinants of cardiovascular risk: the Cardiovascular Health Study.

Titlebeta(2)-Adrenergic receptor polymorphisms and determinants of cardiovascular risk: the Cardiovascular Health Study.
Publication TypeJournal Article
Year of Publication2005
AuthorsHindorff, LA, Heckbert, SR, Psaty, BM, Lumley, T, Siscovick, DS, Herrington, DM, Edwards, KL, Tracy, RP
JournalAm J Hypertens
Volume18
Issue3
Pagination392-7
Date Published2005 Mar
ISSN0895-7061
KeywordsAfrican Americans, Antihypertensive Agents, Arteriosclerosis, Coronary Artery Disease, European Continental Ancestry Group, Female, Genotype, Homozygote, Humans, Hypertension, Incidence, Male, Middle Aged, Polymorphism, Genetic, Receptors, Adrenergic, beta-2, Risk Factors
Abstract<p><b>BACKGROUND: </b>Common Arg16Gly and Gln27Glu polymorphisms of the beta(2)-adrenergic receptor (beta(2)AR) have been associated with hypertension and coronary disease. This analysis of older adults in the Cardiovascular Health Study examined whether these polymorphisms were associated with blood pressure (BP), subclinical atherosclerosis, and, among treated hypertensive individuals, differences in coronary disease risk according to antihypertensive drug class.</p><p><b>METHODS: </b>Altogether, 5249 participants (4441 white and 808 African American, median follow-up time 10.2 years) were genotyped for both polymorphisms. Ankle-arm index (AAI), carotid intima-media thickness (IMT), and brachial flow-mediated dilation were measured cross-sectionally. All estimates were adjusted for ethnicity.</p><p><b>RESULTS: </b>Relative to Gln27 homozygotes, carrying the Glu27 allele was not associated with new-onset hypertension (hazard ratio [HR] = 1.01, 95% confidence interval [CI] = 0.87 to 1.16), BP control (odds ratio [OR] = 0.97, 95% CI = 0.89 to 1.06), AAI (mean difference 0.0042 +/- 0.0052), carotid IMT (mean difference 0.0044 +/- 0.02 mm), or brachial flow-mediated dilation (mean difference in baseline diameter -0.028 +/- 0.036 mm; the most marked of three measures). Among treated hypertensive individuals, coronary disease risk was similar in Glu27 carriers relative to Gln27 homozygotes in subgroups defined by use of beta-blockers (HR = 1.09, 95% CI = 0.64 to 1.87) or other antihypertensive medications (HR = 1.00, 95% CI = 0.78 to 1.28). Results were similar for the Arg16Gly polymorphism.</p><p><b>CONCLUSIONS: </b>The association of beta(2)AR genotype with coronary disease previously reported in this older adult population is not likely to be explained by BP levels, subclinical atherosclerosis, or antihypertensive treatment. Other measures of vascular response, gene-gene or gene-environment interactions, or characteristics developing earlier in life may mediate the association between beta(2)AR genotype and coronary disease and merit further research.</p>
DOI10.1016/j.amjhyper.2004.10.014
Alternate JournalAm J Hypertens
PubMed ID15797659
Grant ListR01 CA149051 / CA / NCI NIH HHS / United States
N01-85086 / / PHS HHS / United States
N01-85085 / / PHS HHS / United States
N01-85079 / / PHS HHS / United States
N01-85081 / / PHS HHS / United States
N01-85080 / / PHS HHS / United States
N01-HC-15103 / HC / NHLBI NIH HHS / United States
N01-85084 / / PHS HHS / United States
N01-HC-35129 / HC / NHLBI NIH HHS / United States
AG15366 / AG / NIA NIH HHS / United States
N01-85083 / / PHS HHS / United States
N01-85082 / / PHS HHS / United States