03325nas a2200421 4500008004100000022001400041245012000055210006900175260001300244300001000257490000700267520209400274653002202368653002802390653002102418653002802439653004002467653001102507653001302518653001502531653001102546653001702557653001402574653000902588653001602597653002602613653003402639653001702673100002302690700002302713700002002736700001902756700002402775700002502799700002202824700002202846856003502868 2005 eng d a0895-706100abeta(2)-Adrenergic receptor polymorphisms and determinants of cardiovascular risk: the Cardiovascular Health Study.0 abeta2Adrenergic receptor polymorphisms and determinants of cardi c2005 Mar a392-70 v183 a
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.
10aAfrican Americans10aAntihypertensive Agents10aArteriosclerosis10aCoronary Artery Disease10aEuropean Continental Ancestry Group10aFemale10aGenotype10aHomozygote10aHumans10aHypertension10aIncidence10aMale10aMiddle Aged10aPolymorphism, Genetic10aReceptors, Adrenergic, beta-210aRisk Factors1 aHindorff, Lucia, A1 aHeckbert, Susan, R1 aPsaty, Bruce, M1 aLumley, Thomas1 aSiscovick, David, S1 aHerrington, David, M1 aEdwards, Karen, L1 aTracy, Russell, P uhttps://chs-nhlbi.org/node/825