β-AR Polymorphisms and Glycemic and Lipid Parameters in Hypertensive Individuals Receiving Carvedilol or Metoprolol

Abstract

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. This was a post hoc analysis of a double-blinded clinical trial of nondiabetic, hypertensive individuals that were randomized to receive carvedilol or metoprolol succinate. Fasting glucose, insulin, and lipid levels were measured at baseline, 3 months, 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 (p(interaction)). The 322 subjects were mean (s.d.) 51.5 (11.2) years old. After 6 months, insulin levels increased by 35.6% on metoprolol and 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 higher triglycerides levels. An interaction between the Arg16Gly SNP and treatment was identified (p(int) = 0.048). These data suggest that insulin and triglycerides may be influenced by β2-AR polymorphisms in patients taking β blockers.