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 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). Results 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). Conclusions These data suggest that insulin and triglycerides may be influenced by Β2-AR polymorphisms in patients taking Β blockers.
Bibliographical noteFunding Information:
acknowledgment: this work was funded by glaxosmithKline and NIH 1uL1RR025011.
- blood pressure
- β-adrenergic receptor gene polymorphism