The Trp64Arg Polymorphism of the β 3-Adrenergic Receptor Gene Is Not Associated with Obesity or Type 2 Diabetes Mellitus in a Large Population-Based Caucasian Cohort

Abstract

The beta3-adrenergic receptor (3-BAR) is assumed to play a role in the regulation of energy balance by increasing lipolysis and thermogenesis. A recently detected allelic polymorphism (Trp64Arg polymorphism) has been suggested to contribute to the development of obesity and non-insulin-dependent diabetes mellitus. We examined the prevalence of the two 3-BAR alleles in Germany and looked for associations between 3-BAR genotype and metabolic disorders (obesity and type 2 diabetes mellitus). From over 6450 participants in the Diabetomobile Study, a nationwide epidemiologic study on the prevalence of metabolic disorders (carried out from 1993 to 1996 in Germany), 1259 participants were randomly chosen. The 3-BAR genotype status was determined by 3-BAR gene-specific genomic PCR and consecutive restriction fragment length polymorphism analysis. The frequencies of the different genotypes in the examined cohort were as follows: Trp64/Trp64, 88.3%; Trp64/Arg64, 10.8%; and Arg64/ Arg64, 0.8%. No significant differences between the different genotypes were found when comparing age, body mass index, weight, total and high-density lipoprotein (HDL) cholesterol, fasting insulin, HbA11, and blood pressure; neither did the type 2 diabetes mellitus participants in the different genotype groups differ significantly in terms of age of diabetes onset or HbA11. This is the largest population-based study on the Trp64Arg polymorphism reported yet. The Arg64 allele of the 3-BAR gene was found commonly in Germany. In our cohort, no significant associations between the Arg64 allele and metabolic disorders (e.g. obesity, type 2 diabetes mellitus, dyslipidemia, or hypertension) were detected.