ADRB1的功能多态性(Ser49Gly和Arg389Gly)与心血管和β受体阻滞剂反应结果相关。在这里,我们检查了这些多态性与主要不良心血管事件(MACE)的关系,对有中风史的患者进行β受体阻滞剂治疗和不进行分层。
纳入SPS3试验(皮质下小卒中的二级预防)高血压遗传亚研究的9126名参与者。MACE包括中风,心肌梗塞,和全因死亡。使用Kaplan-Meier和多变量Cox回归分析。因为MACE的主要成分是缺血性卒中,我们在NINDS(美国国家神经疾病和卒中研究所)SIGN(卒中遗传学网络)中的41475名欧洲和非洲血统个体中检测了Ser49Gly与缺血性卒中的相关性.
Gly49等位基因携带者的MACE高于Ser49Ser基因型携带者(10.5%对5.4%,对数秩P=0.005)。Gly49携带者状态与MACE相关(风险比,1.62;95%置信区间,1.00-2.68)和缺血性卒中(风险比,1.81;95%置信区间,1.01-3.23)在SPS3和小动脉缺血性卒中(比值比,1.14;95%置信区间,1.03-1.26)在SiGN中。在SPS3中,β受体阻滞剂治疗的Gly49携带者与非β受体阻滞剂治疗的个体和非携带者相比,MACE增加(风险比,2.03;95%置信区间,1.20-3.45)。未观察到与Arg389Gly多态性的关联。
在既往有小动脉缺血性卒中的个体中,ADRB1Gly49多态性与MACE,特别是小动脉缺血性中风,在β受体阻滞剂治疗的个体中可能增加的风险。需要进一步的研究来确定ADRB1基因型对缺血性卒中患者β受体阻滞剂的益处。
URL:http://www。临床试验.gov.唯一标识符:NCT00059306。
Functional polymorphisms (Ser49Gly and Arg389Gly) in ADRB1 have been associated with cardiovascular and β-blocker response outcomes. Herein we examined associations of these polymorphisms with major adverse cardiovascular events (MACE), with and without stratification by β-blocker treatment in patients with a history of stroke.
Nine hundred and twenty-six participants of the SPS3
trial\'s (Secondary Prevention of Small Subcortical Strokes) genetic substudy with hypertension were included. MACE included stroke, myocardial infarction, and all-cause death. Kaplan-Meier and multivariable Cox regression analyses were used. Because the primary component of MACE was ischemic stroke, we tested the association of Ser49Gly with ischemic stroke among 41 475 individuals of European and African ancestry in the NINDS (National Institute of Neurological Disorders and Stroke) SiGN (Stroke Genetics Network).
MACE was higher in carriers of the Gly49 allele than in those with the Ser49Ser genotype (10.5% versus 5.4%, log-rank P=0.005). Gly49 carrier status was associated with MACE (hazard ratio, 1.62; 95% confidence interval, 1.00-2.68) and ischemic stroke (hazard ratio, 1.81; 95% confidence interval, 1.01-3.23) in SPS3 and with small artery ischemic stroke (odds ratio, 1.14; 95% confidence interval, 1.03-1.26) in SiGN. In SPS3, β-blocker-treated Gly49 carriers had increased MACE versus non-β-blocker-treated individuals and noncarriers (hazard ratio, 2.03; 95% confidence interval, 1.20-3.45). No associations were observed with the Arg389Gly polymorphism.
Among individuals with previous small artery ischemic stroke, the ADRB1 Gly49 polymorphism was associated with MACE, particularly small artery ischemic stroke, a risk that may be increased among β-blocker-treated individuals. Further research is needed to define β-blocker benefit among ischemic stroke patients by ADRB1 genotype.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059306.