University of Wisconsin School of Pharmacy, Madison, WI, USA.
Am J Hypertens. 2012 Aug;25(8):920-6. doi: 10.1038/ajh.2012.54. Epub 2012 May 31.
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.
β受体阻滞剂治疗和β肾上腺素能受体（β-AR）多态性与血糖和血脂水平升高有关。我们研究了常见的β1和β2-AR 单核苷酸多态性（SNP）与代谢和脂质变量的关系，并检查了与β受体阻滞剂治疗分配的相互作用，以影响这些参数。
这是一项对接受卡维地洛或琥珀酸美托洛尔的非糖尿病、高血压个体进行的双盲临床试验的事后分析。在基线、3 个月和 6 个月时测量空腹血糖、胰岛素和血脂水平。确定β1-AR SNP Ser49Gly 和 Gly389Arg 以及β2-AR Arg16Gly 和 Gln27Glu 的基因型。使用多变量混合模型来检查β-AR 多态性、代谢参数与β受体阻滞剂治疗（p（交互））之间的关系。
322 名受试者的平均（标准差）年龄为 51.5（11.2）岁。服用美托洛尔 6 个月后，胰岛素水平升高 35.6%，服用卡维地洛后升高 9.9%（P = 0.015）。在单变量模型中，与 Glu27Glu 基因型相比，Gln27Gln 基因型在接受β受体阻滞剂治疗时具有更高的总胰岛素水平（P = 0.006）。Arg16Gly（P = 0.012）和 Gln27Glu（P = 0.037）SNP 均与较高的甘油三酯水平相关。还确定了 Arg16Gly SNP 与治疗之间的相互作用（p(int) = 0.048）。
这些数据表明，接受β受体阻滞剂治疗的患者的胰岛素和甘油三酯水平可能受到β2-AR 多态性的影响。
