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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Hindorff
Lucia A
LA
Department of Epidemiology, University of Washington, Seattle, Washington, USA. lah@u.washington.edu
Heckbert
Susan R
SR
Psaty
Bruce M
BM
Lumley
Thomas
T
Siscovick
David S
DS
Herrington
David M
DM
Edwards
Karen L
KL
Tracy
Russell P
RP
D001741:Black or African American / Q000706:statistics & numerical data; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000453:epidemiology / Q000235:genetics; D003324:Coronary Artery Disease / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000453:epidemiology* / Q000235:genetics*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012307:Risk Factors; D044465:White People / Q000706:statistics & numerical data
D000959:Antihypertensive Agents; D018343:Receptors, Adrenergic, beta-2