Association of the β3-adrenergic receptor Trp64Arg polymorphism with common metabolic traits: Studies of 7605 middle-aged white people
Section snippets
Study population
Genotyping of the ADRB3 Trp64Arg (rs4994) variant was performed in a total of 7605 Danish white subjects. Three study populations were included in the analyses:
(1) 6215 middle-aged Danes from the greater Copenhagen area sampled at Research Centre for Prevention and Health (the population-based Inter99 cohort) [24]. These individuals included 3045 men and 3170 women aged 46 ± 8 years (mean ± SD) and having a BMI of 26.3 ± 4.6 kg/m2. The prevalence of fasting normoglycaemia and normal glucose tolerance
Results
Heterogeneity between the three study populations with respect to the Arg-allele or genotype frequencies was examined and no heterogeneity was identified. Therefore, combined analyses were conducted. The ADRB3 Trp64Arg allele frequency in 7605 Danes was 7.1% (95% CI: 6.7–7.5%). The Trp64Arg variant was examined for differences in genotype distribution and allele frequency between obese and non-obese individuals (data not shown); but no significant differences were detected. The same analysis
Discussion
The minor allele frequency of the ADRB3 Trp64Arg polymorphism observed in this study population was 0.07 (95% CI: 0.067–0.075) which is consistent with the allele frequency in comparable populations composed of mixed whites, white Americans, and Germans [3], [8], [22]. No consistent and convincing association of the Trp64Arg variant was detected in relation to the pathogenesis of obesity. The power of the present study to detect the effect previously seen [10] was more than 99%. The lack of
Acknowledgments
The study was supported by the Danish Medical Research Council, the Danish Diabetes Association, the Danish Heart Foundation, the Velux Foundation, the European Economic Community (Exgenesis LSHM-CT-2004-005272) and the FOOD Study Group/the Danish Ministry of Food, Agriculture and Fisheries and Ministry of Family and Consumer Affairs (2101-05-0044). The authors wish to thank Annemette Forman, Inge-Lise Wantzin, Tina Lorentzen, and Marianne Stendal for technical assistance and Grete Lademann for
References (52)
- et al.
Fat cell adrenergic receptors and the control of white and brown fat cell function
J. Lipid. Res.
(1993) - et al.
A mutation in the β3-adrenergic receptor gene is associated with obesity and hyperinsulinemia in Japanese subjects
Biochem. Biophys. Res. Commun.
(1995) - et al.
Association of β3-adrenergic receptor gene polymorphism with insulin resistance in Japanese-American men
Metabolism
(1999) - et al.
Targeted disruption of the β3-adrenergic receptor gene
J. Biol. Chem.
(1995) - et al.
The codon 64 polymorphism of the β3-adrenergic receptor gene is not associated with coronary heart disease or insulin resistance in nondiabetic subjects and non-insulin-dependent diabetic patients
Metabolism
(1999) - et al.
The significance of the Trp 64 Arg mutation of the β3-adrenergic receptor gene in impaired glucose tolerance, non-insulin-dependent diabetes mellitus, and insulin resistance in Japanese subjects
Metabolism
(1998) - et al.
β3-adrenergic receptor gene polymorphism is not a major genetic determinant of obesity and diabetes in Japanese general population
Diabetes. Res. Clin. Pract.
(1997) - et al.
Prevalence of the Trp64Arg missense mutation of the β3-adrenergic receptor gene in Japanese subjects
Metabolism
(1997) - et al.
Tissue distribution of β3-adrenergic receptor mRNA in man
J. Clin. Invest.
(1993) - et al.
Time of onset of non-insulin-dependent diabetes mellitus and genetic variation in the β3-adrenergic receptor gene
N. Engl. J. Med.
(1995)