Arg₃₈₉Gly β₁-adrenoceptor polymorphism varies in frequency among different ethnic groups but does not alter response in vivo

There are marked interethnic differences in β₁-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 β₁-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 β₁-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 β₁-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 β₁-adrenoceptor.