β3-Adrenergic receptor Trp64Arg polymorphism does not predict incident CHD or carotid intima-media thickness in a community-based sample of whites: the ARIC study

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.

Effect of Trp64Arg mutation of the β3‐adrenergic receptor gene and C161T substitution of the peroxisome proliferator activated receptor γ gene on obesity in Japanese children

“…There have been many studies about the relationship between Trp64Arg and obesity in adults. [4][5][6][7][8][9][10][11][12][13] Recently, a meta-analysis of the studies in Japanese adults was reported. 31 According to the report, Trp64Arg was associated with BMI in Japanese adults.…”

“…7 Other studies have indicated that Trp64Arg is associated with coronary heart disease (CHD). 8 However, several other studies have suggested that Trp64Arg is not associated with obesity, CHD or type 2 DM [9][10][11][12][13] Thus, it is still controversial whether Trp64Arg is associated with these metabolic diseases.…”

Heritability of Carotid Artery Intima-Medial Thickness in Type 2 Diabetes

“…Candidate genes that have been examined include apoE, [17][18][19][20] paraoxonase, [21][22][23][24] ACE, 22,[25][26][27] cholesterol ester transfer protein, 28 ␤ 3 -adrenergic receptor, 29 and methylenetetrahydrofolate. 22,30,31 The inconsistency among the results from these The ␤ coefficients represent the change in IMT for a 1-SD increase in the predictor.…”

T64A polymorphism in β3‐adrenergic receptor gene (ADRB3) and coronary heart disease: a case‐cohort study and meta‐analysis

“…After Higashi et al [7] had published their data showing that the frequency of the Trp64Arg variant of the ADRB3 gene polymorphism was higher in 83 Japanese patients with CHD (0.247) versus 107 control subjects (0.145), several efforts have been undertaken to replicate these results in similar or different populations [8][9][10][11][12][13][14][15]. Stangl et al so far have performed the largest study, in a cross-sectional design amongst 992 CHD cases and 988 controls in Germany [11].…”

“…Given the importance of obesity, diabetes mellitus and hypertension in the occurrence of coronary heart disease (CHD), these findings suggest that this polymorphism may confer an increased risk of CHD. In contrast to a first report in a small population on the association of Trp64Arg polymorphism with CHD [7], subsequent studies have shown no association [8][9][10][11][12][13][14][15]. We set out to investigate the relationship of Trp64Arg polymorphism in the ADRB3 gene on the occurrence of acute myocardial infarction (AMI) and CHD in middle-aged Dutch women.…”