Arg389Gly ??1-adrenoceptor polymorphism varies in frequency among different ethnic groups but does not alter response in vivo

Abstract

There are marked interethnic differences in beta 1-adrenoceptor-mediated responsiveness, with sensitivity decreased in African-Americans and increased in Chinese compared with Caucasians. Therefore, the frequency of a common naturally occurring polymorphism of the human beta 1-adrenoceptor gene (Arg389Gly), which has functional importance in vitro, was determined in 194 African-Americans, 316 Caucasian-Americans, 221 Hispanic-Americans and 142 Chinese. African-Americans were found to have a significantly lower frequency of the Arg389 allele than the other three ethnic groups (all P < 0.01). In the populations studied, the order of the distribution of the Arg389 allele was: Chinese (74%) > Caucasians (72%) > Hispanics (67%) > African-Americans (58%). To determine the functional significance of the Arg389Gly beta 1-adrenoceptor polymorphism, in-vivo heart rate responses to exercise were compared in healthy subjects homozygous for the Arg (n = 9) and Gly (n = 8) alleles. Heart rate response to exercise was not affected by genotype (P = 0.4). Although ethnic differences in the frequency of the beta 1-adrenoceptor Arg389Gly polymorphism exist, the polymorphism does not appear to have functional significance in healthy subjects and therefore may not contribute to ethnic differences in response to drugs acting through the beta 1-adrenoceptor.

Beta1‐adrenergic receptor gene polymorphisms and response to Beta1‐adrenergic receptor blockade in patients with essential hypertension

“…16 Recently, however, two studies found no difference in exercise-induced HR and SBP response among healthy subjects who were homozygous for the Arg389 or Gly389 alleles, suggesting a limited functional importance of this polymorphism in vivo. 17,18 In our study, we observed no Arg389Gly genotype-dependent difference in baseline blood pressure or HR, nor did we find any significant differences between reduction of blood pressure and HR during treatment with the ␤ 1 -AR blocker atenolol. This suggests that this polymorphism is of at least no major importance in determining the response to this antihypertensive drug.…”

Influence of phenotype and pharmacokinetics on β-blocker drug target pharmacogenetics

“…[4][5][6][9][10][11] Similarly consistent with other reports in the literature, we found no association between heart rate response to b-adrenergic receptor antagonists and codon 389 genotype. [4][5][6]12 With regard to associations with codon 49, our results agree with Ranade et al 11 and find a significant association between untreated resting heart rate and codon 49 genotype in hypertensive individuals.…”

“…The racial/ ethnic breakdown of the overall population was 41 Caucasian, 10 African American, and three Hispanic/Latino. More African American subjects were Gly389 carriers (15 Caucasian/eight African American/two Hispanic/Latino) than Arg389 homozygotes (26 Caucasian/two African American/ one Hispanic/Latino) (P ¼ 0.041), which is consistent with known racial differences in codon 389 allele frequencies 9 and the a priori rationale for including race as a covariate in all analyses (see Materials and methods). There were no racial differences in codon 49 allele frequencies.…”

Markedly reduced effects of (−)‐isoprenaline but not of (−)‐CGP12177 and unchanged affinity of β‐blockers at Gly389‐β1‐adrenoceptors compared to Arg389‐β1‐adrenoceptors

“…Exercise-induced increase in heart rate appeared to be unaffected by the Arg389Gly polymorphism (Buscher et al, 2001;Xie et al, 2001) in healthy volunteers. In contrast, heart failure patients homozygous for the Gly389 polymorphism had depressed exercise performance compared to those with Arg389-b 1 -adrenoceptors (Wagoner et al, 2002).…”