A polymorphism in the α1 adrenergic receptor is associated with resting heart rate
Journal
American Journal of Human Genetics
Journal Volume
70
Journal Issue
4
Pages
935-942
Date Issued
2002
Author(s)
Ranade K.
Jorgenson E.
Sheu W.H.-H.
Pei D.
Hsiung C.A.
Chen Y.-D.I.
Pratt R.
Olshen R.A.
Curb D.
Cox D.R.
Botstein D.
Risch N.
Abstract
Resting heart rate is significantly associated with cardiovascular morbidity and mortality. However, the extent to which resting heart rate is genetically determined is poorly understood, and no genes have been found that contribute to variation in resting heart rate. Because signaling through the β1 adrenergic receptor is a key determinant of cardiac function, we tested whether polymorphisms in this receptor are associated with resting heart rate. A cohort of >1,000 individuals of Chinese and Japanese descent, from nuclear families, was genotyped for two polymorphisms, resulting in a serine/glycine substitution at amino acid 49 (Ser49Gly) and an arginine/glycine substitution at residue 389 (Arg389Gly), in the β1 adrenergic receptor. For comparison, polymorphisms in the β2 and β3 adrenergic receptors were also evaluated. The Ser49Gly polymorphism was significantly associated (P =. 0004) with resting heart rate, independent of other variables, such as body-mass index, age, sex, ethnicity, exercise, smoking, alcohol intake, hypertension status, and treatment with beta blockers. The data support an additive model in which individuals heterozygous for the Ser49Gly polymorphism had mean heart rates intermediate to those of either type of homozygote, with Ser homozygotes having the highest mean heart rate and with Gly homozygotes having the lowest. Neither the Arg389Gly polymorphism in the β1 adrenergic receptor nor polymorphisms in the β2 and β3 adrenergic receptors were associated with resting heart rate. The heritability of heart rate was 39.7% ± 7.1% (P < 10-7).
SDGs
Other Subjects
arginine; beta 1 adrenergic receptor; beta adrenergic receptor blocking agent; gene product; glycine; serine; beta 1 adrenergic receptor; adult; age; alcohol consumption; amino acid substitution; article; body mass; cardiovascular disease; correlation analysis; ethnology; exercise; female; gene function; genetic polymorphism; genotype; heart function; heart rate variability; heterozygosity; homozygosity; human; hypertension; major clinical study; male; morbidity; mortality; pathogenesis; priority journal; rest; sex; smoking habit; Asian; blood pressure; China; drinking behavior; ethnic group; genetics; heart rate; homozygote; Japan; middle aged; sex difference; single nucleotide polymorphism; smoking; Age Factors; Alcohol Drinking; Asian Continental Ancestry Group; Blood Pressure; Body Mass Index; China; Ethnic Groups; Exercise; Female; Heart Rate; Homozygote; Humans; Hypertension; Japan; Male; Middle Aged; Polymorphism, Single Nucleotide; Receptors, Adrenergic, beta-1; Sex Factors; Smoking
Type
journal article