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

Abstract

Aims/hypothesis: Functional and common Arg16Gly and Gln27Glu polymorphisms have been identified in ADRB2, the gene encoding the β2- 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 β2-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 β2-adrenergic receptor and obesity, hypertension or type 2 diabetes. © 2007 Springer-Verlag.