Background β-blocker therapy and β-adrenergic receptor (β-AR) polymorphisms are associated with increases in glucose and lipid levels. We investigated associations of common β1 and β2- AR single nucleotide polymorphisms (SNPs) with metabolic and lipid variables, and examined interactions with β-blocker treatment assignment to affect these parameters. Methods This was a Post hoc analysis of a double-blinded clinical trial of non-diabetic, hypertensive individuals that were randomized to receive carvedilol or metoprolol succinate. Fasting glucose, insulin, and lipid levels were measured at baseline, 3, and after 6 months. Genotypes for β1-AR SNPs Ser49Gly & Gly389Arg and β2-AR Arg16Gly & Gln27Glu were determined. Multivariable mixed models were used to examine associations between β-AR polymorphisms, metabolic parameters, and SNP interactions with β-blocker therapy (pinteraction). Results The 322 subjects were mean (standard deviation) 51.5 (11.2) years old. After 6 months, insulin levels increased by 35.6% on metoprolol but decreased by 9.9% on carvedilol (p=0.015). In univariate models, the Gln27Gln genotype had higher overall insulin levels with β-blockade compared to the Glu27Glu genotype (p=0.006). Both Arg16Gly (p=0.012) and Gln27Glu (p=0.037) SNPs were associated with triglycerides levels. An interaction between the Arg16Gly SNP and treatment was identified (pint=0.048). Conclusions These data suggest that insulin and triglycerides may be influenced by β2-AR polymorphisms in patients taking β–blockers.

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