EXPRESSION OF THE BETA(3)-ADRENOCEPTOR GENE POLYMORPHISM (TRP64ARG) IN OBESE-DIABETIC AND NONDIABETIC SUBJECTS

1, A missense mutation (Trp64Arg) in the beta(3)-adrenoceptor (beta(3) -AR) gene has been associated with weight gain, insulin resistance and earlier-onset non-insulin-dependent diabetes mellitus (NIDDM), but th e strength of these associations varies considerably between populatio ns and the functional significance of Trp64Arg remains unclear. 2, The Trp64Arg mutation was investigated in obese NIDDM (n = 50) and obese non-diabetic (n = 53) subjects by polymerase chain reaction (PCR) ampl ification of genomic DNA and digestion of the 210 bp product by BstOI, The Arg allele was found in 22.3% of all subjects, but there were no homozygotes for the mutation, Non-diabetic subjects heterozygous for t he mutation were more obese and Trp/Arg diabetics had a slightly young er age of onset of NIDDM (47 vs 51 years, respectively), but there wer e no significant differences in mutation frequency between the two gro ups. Metabolic parameters (e,g, fasting lipids and glycaemic control) were similar among diabetic subjects with and without the Trp64Arg mut ation, 3, In conclusion, the frequency of the Trp64Arg mutation of the beta(3)-AR higher in this obese population compared with some previou s studies, but there was no evidence that Trp64Arg confers an increase d susceptibility to NIDDM among obese insulin-resistant subjects or th at diabetics with the mutation fare worse in terms of lipid or glucose metabolism.