A polymorphism in the beta1 adrenergic receptor is associated with resting heart rate.
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 beta1 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 beta1 adrenergic receptor. For comparison, polymorphisms in the beta2 and beta3 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 beta1 adrenergic receptor nor polymorphisms in the beta2 and beta3 adrenergic receptors were associated with resting heart rate. The heritability of heart rate was 39.7% +/- 7.1% (P<10-7).
Ranade
Koustubh
K
Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA. koustubh.ranade@bms.com
Jorgenson
Eric
E
Sheu
Wayne H-H
WH
Pei
Dee
D
Hsiung
Chao Agnes
CA
Chiang
Fu-tien
FT
Chen
Yii-der I
YD
Pratt
Richard
R
Olshen
Richard A
RA
Curb
David
D
Cox
David R
DR
Botstein
David
D
Risch
Neil
N
D000367:Age Factors; D000428:Alcohol Drinking; D044466:Asian People / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics; D015992:Body Mass Index; D002681:China / Q000208:ethnology; D005006:Ethnicity / Q000235:genetics; D015444:Exercise; D005260:Female; D006339:Heart Rate / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D006973:Hypertension / Q000235:genetics; D007564:Japan / Q000208:ethnology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D012737:Sex Factors; D012907:Smoking
D018342:Receptors, Adrenergic, beta-1