Interactive Effects of Common β2-Adrenoceptor Haplotypes and Age on Susceptibility to Hypertension and Receptor Function

Few studies have examined to what extent genetic variants of the β2-adrenoceptor (ADRB2) are involved in the development of hypertension with age, although β2-adrenergic receptor responsiveness declines in older subjects. To investigate this, 10 common single-nucleotide polymorphisms (SNPs) in the p...

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Published in:Hypertension (Dallas, Tex. 1979) Tex. 1979), 2005-08, Vol.46 (2), p.301-307
Main Authors: Bao, Xuping, Mills, Paul J, Rana, Brinda K, Dimsdale, Joel E, Schork, Nicholas J, Smith, Douglas W, Rao, Fangwen, Milic, Milos, O’Connor, Daniel T, Ziegler, Michael G
Format: Article
Language:English
Subjects:
Antihypertensive agents
Arterial hypertension. Arterial hypotension
Biological and medical sciences
Blood and lymphatic vessels
Cardiology. Vascular system
Cardiovascular system
Clinical manifestations. Epidemiology. Investigative techniques. Etiology
Medical sciences
Pharmacology. Drug treatments
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Summary:Few studies have examined to what extent genetic variants of the β2-adrenoceptor (ADRB2) are involved in the development of hypertension with age, although β2-adrenergic receptor responsiveness declines in older subjects. To investigate this, 10 common single-nucleotide polymorphisms (SNPs) in the promoter and coding regions of the ADRB2 gene were genotyped in an unrelated population consisting of 2 ethnic groupsEuropean American (EA; n=610) and African American (AA; n=420). ADRB2 haplotypes were estimated by expectation maximization (EM) algorithm–based methods. In the general population for EAs and AAs, the variants of the ADRB2 gene, including the individual SNPs and their haplotypes, were not associated with hypertension. However, there was a significant interaction between age and one of the common haplotypes (haplotype 1) in EAs (P=0.01). Haplotype 1 was associated with protection against hypertension in young (≤50 years of age) but not in old (>50 years of age) EAs (odds ratio, 0.5; 95% confidence interval, 0.27 to 0.91; P=0.02). This age-specific effect was further supported by the observations that young subjects carrying ≥1 copy of haplotype 1 had significantly lower diastolic blood pressure and nearly 2-fold higher ADRB2 binding density than the noncarriers (P
ISSN:0194-911X
1524-4563
DOI:10.1161/01.HYP.0000175842.19266.95