Studies of the associations between functional β2-adrenergic receptor variants and obesity, hypertension and type 2 diabetes in 7,808 white subjects

Aims/hypothesis Functional and common Arg16Gly and Gln27Glu polymorphisms have been identified in ADRB2, the gene encoding the beta(2)-adrenergic receptor. These variants have previously been examined for association with obesity, hypertension and diabetes with inconclusive results. Materials and methods We investigated both of these variants in 7,808 unrelated, middle-aged white people for their association with obesity in a case-control study, quantitative trait analysis and meta-analysis. Moreover, both variants were investigated for their potential influence on measures of hypertension and type 2 diabetes by case-control and quantitative trait analyses. Results The present study did not find consistent evidence for an association of these beta(2)-adrenergic receptor variants with obesity or hypertension; neither did the quantitative trait analyses show any effect of the variants on obesity-related traits. However, both the Gly allele of the Arg16Gly variant and the Glu allele of the Gln27Glu variant showed nominal association with systolic blood pressure. Furthermore, there was a nominal association of the Arg16 allele frequency and genotype distribution with type 2 diabetes; however, no influence on quantitative biochemical phenotypes related to type 2 diabetes was found. A nominal association of the Arg/Gly genotype with the metabolic syndrome was also observed (p = 0.003). Logistic regression analyses provided no evidence of a synergistic or an additive effect of these variants on obesity, hypertension or diabetes. Conclusions/interpretation After studying 7,808 middle-aged white subjects, we were unable to demonstrate any consistent associations between two common amino acid polymorphisms of the beta(2)-adrenergic receptor and obesity, hypertension or type 2 diabetes.