Association of polymorphisms in the beta 2-adrenergic receptor gene with obesity, hypertriglyceridaemia, and diabetes mellitus

To assess the role of polymorphisms in the beta 2-adrenergic receptor gene in the development of obesity and obesity-related metabolic disorders, we a nalysed Arg16Gly, Gln27Glu, and Thr164Ile polymorphisms in 400 non-obese su bjects (body mass index <27 kg/m(2)) and 108 obese subjects (body mass inde x greater than or equal to 27 kg/m(2)). The Gln27Glu substitution was twice as common in obese subjects as in non-obese subjects (0.14 vs 0.07, p = 0. 001, odds ratio 2.14, 95% confidence interval 1.35-3.41). The frequency of the Glu27 allele was also higher in patients with Type II (non-insulin-depe ndent) diabetes mellitus than nondiabetic subjects (0.14 vs 0.07, p = 0.001 , odds ratio 2.13, 95% confidence interval 1.34-3.41). Analysis of variance of multiple variables showed an association between 2-h post-load glucose concentrations and body mass index but not with the Glu27 variant, suggesti ng that the association with diabetes could be secondary to obesity. Obese subjects carrying the variant allele had higher concentrations of serum tri glyceride than obese subjects homozygous for the wild type allele (2.68 +/- 1.90 vs 1.18 +/- 1.15 mmol/l, p = 0.02). Conversely, the frequency of Gly1 6 homozygotes was lower in obese women when compared with non-obese women ( 11% vs 28%, p = 0.01, odds ratio 0.30, 95% confidence interval 0.12-0.75), although the association was not present in male subjects. Thr164Ile substi tution was not detected in the subjects of this study. These observations s uggest that the amino-terminal polymorphisms of the beta 2-adrenergic recep tor gene could be involved in the molecular pathogenesis of obesity and hyp ertriglyceridaemia, and thereby the development of Type II diabetes mellitu s.