Title | Beta3-adrenergic receptor Trp64Arg polymorphism does not predict incident CHD or carotid intima-media thickness in a community-based sample of whites: the ARIC study. Atherosclerosis Risk in Communities. |
Publication Type | Journal Article |
Year of Publication | 1999 |
Authors | Morrison AC, Brancati FL, Folsom AR, Smith L, Boerwinkle E |
Journal | Hum Genet |
Volume | 105 |
Issue | 4 |
Pagination | 314-9 |
Date Published | 1999 Oct |
ISSN | 0340-6717 |
Keywords | Aged, Alleles, Amino Acid Substitution, Arteriosclerosis, Base Sequence, Carotid Arteries, Cohort Studies, Coronary Disease, DNA Primers, Female, Gene Frequency, Humans, Male, Middle Aged, Phenotype, Point Mutation, Polymorphism, Genetic, Receptors, Adrenergic, beta, Receptors, Adrenergic, beta-3, Risk Factors, United States, White People |
Abstract | The beta3-adrenergic receptor (beta3-AR) is expressed in adipose tissue and plays a significant role in controlling energy expenditure through the regulation of lipolysis and thermogenesis. The possible clinical importance of the beta3-AR Trp64Arg polymorphism has prompted us to investigate the association between it and the extent of atherosclerosis and risk of incident coronary heart disease (CHD). The ability of the beta3-AR Trp64Arg polymorphism to predict the extent of atherosclerosis and incident CHD has been evaluated in participants of the Atherosclerosis Risk in Communities (ARIC) study. Incident CHD cases (n=271) were compared with a stratified random sample of the ARIC cohort (n=700). Comparisons were also made between a group with increased intimamedia thickness (IMT) of the carotid artery walls, but without prevalent CHD (n=324), and a thin-walled control group (n=407). The frequency of the Arg64 allele was 0.081 and 0.069 in the incident CHD cases and cohort sample, respectively, and 0.062 and 0.057 in the IMT cases and thin-walled controls, respectively. Comparison of incident CHD cases and the cohort sample by Cox proportional hazards modeling indicated that the Arg64 allele was not a significant predictor of incident CHD, either alone (RR=0.99, P=0.98) or after inclusion of body mass index (BMI) and fasting insulin and glucose measurements (RR=1.02, P=0.93). A comparison of IMT cases and thin-walled controls by multivariate logistic regression analysis suggested that the Arg64 allele was not a significant predictor of carotid artery intima-media thickness when evaluated alone (OR=1.32, P=0.29) or after BMI and fasting insulin and glucose measurements were added to the model (OR=1.28, P=0.35). We infer that the beta3-AR Trp64Arg polymorphism is not a major predictor of atherosclerosis or incident CHD in this sample of middle-aged white Americans. |
DOI | 10.1007/s004399900096 |
Alternate Journal | Hum Genet |
PubMed ID | 10543398 |
Grant List | N01-HC-55015 / HC / NHLBI NIH HHS / United States N01-HC-55016 / HC / NHLBI NIH HHS / United States N01-HC-55018 / HC / NHLBI NIH HHS / United States |