THE TRP64ARG POLYMORPHISM OF THE BETA-3-ADRENERGIC RECEPTOR GENE IS NOT ASSOCIATED WITH OBESITY OR TYPE-2 DIABETES-MELLITUS IN A LARGE POPULATION-BASED CAUCASIAN COHORT

The beta 3-adrenergic receptor (3-BAR) is assumed to play a role in th e regulation of energy balance by increasing lipolysis and thermogenes is. A recently detected allelic polymorphism (Trp64Arg polymorphism) h as 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-BA R genotype and metabolic disorders (obesity and type 2 diabetes mellit us). From over 6450 participants in the Diabetomobile Study, a nationw ide epidemiologic study on the prevalence of metabolic disorders (carr ied out from 1993 to 1996 in Germany), 1259 participants were randomly chosen. The 3-BAR genotype status was determined by 3-BAR gene-specif ic genomic PCR and consecutive restriction fragment length polymorphis m analysis. The frequencies of the different genotypes in the examined cohort were as follows: Trp64/Trp64, 88.3%; Trp64/Arg64, 10.8%; and A rg64/ Arg64, 0.8%. No significant differences between the different ge notypes were found when comparing age, body mass index, weight, total and high-density lipoprotein (HDL) cholesterol, fasting insulin, HbA1( c), and blood pressure; neither did the type 2 diabetes mellitus parti cipants in the different genotype groups differ significantly in terms of age of diabetes onset or HbA1(c). This is the largest population-b ased study on the Trp64Arg polymorphism reported yet. The Arg64 allele of the 3-BAR gene was found commonly in Germany. In our cohort, no si gnificant associations between the Arg64 allele and metabolic disorder s (e.g. obesity, type 2 diabetes mellitus, dyslipidemia, or hypertensi on) were detected.