β2-adrenergic receptor genetic variants and risk of sudden cardiac death
β2-adrenergic receptor genetic variants and risk of sudden cardiac death
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DOI：
10.1161/circulationaha.105.582833
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发表时间：
2006-04-18
期刊：
影响因子：
37.8
通讯作者：
Heckbert, SR
中科院分区：
文献类型：
--
作者：
Sotoodehnia, N;Siscovick, DS;Heckbert, SR
交感神经激活影响室性心律失常和心脏性猝死（SCD）的风险，部分由β 2肾上腺素能受体（B2 AR）介导。我们调查是否在B2 AR基因的变异与SCD risk.Methods和结果-在这项研究中，4441白色和808黑人心血管健康研究（CHS）参与者进行了前瞻性随访SCD和基因型B2 AR Gly 16 Arg和Gln 27 Glu多态性。该研究在SCD的基于人群的病例对照研究心脏骤停血液研究（CABS）中在155例病例和144例对照白色受试者中重复。在CHS中，Gly 16和Gln 27等位基因频率在白色人群中分别为62.4%和57.1%，在黑人人群中分别为50.1%和81.4%。中位随访时间为11.1年，白色和黑人参与者分别发生了156和39起SCD事件。Gln 27 Glu变异与SCD风险相关（一般模型P = 0.008）。Gln 27纯合子参与者的SCD风险高于Glu 27携带者（种族调整风险比[HR]，1.56; 95%置信区间[CI]，1.17至2.09; P = 0.003）。白色受试者（HR，1.62; 95% CI，1.18 - 2.23）和黑人受试者（HR，1.23; 95% CI，0.61 - 2.48）之间的风险增加无显著差异，尽管黑人的置信区间较宽。在CABS复制研究中，Gln 27纯合子参与者同样比Glu 27携带者有更高的SCD风险（比值比，1.64; 95%CI，1.02至2.63; P = 0.040）。Gly 16 Arg是不相关的SCD风险在either study.Conclusions -Gln 27纯合子个体有SCD的风险增加，在2个研究人群。我们的研究结果表明，B2 AR在人类SCD中发挥作用。研究B2 AR基因内的遗传变异可能有助于识别SCD风险增加的患者。
Background - Sympathetic activation influences the risk of ventricular arrhythmias and sudden cardiac death (SCD), mediated in part by the beta 2-adrenergic receptor (B2AR). We investigated whether variation in the B2AR gene is associated with SCD risk.Methods and Results - In this study, 4441 white and 808 black Cardiovascular Health Study (CHS) participants were followed up prospectively for SCD and genotyped for B2AR Gly16Arg and Gln27Glu polymorphisms. The study was replicated in 155 case and 144 control white subjects in a population-based case-control study of SCD, the Cardiac Arrest Blood Study ( CABS). In CHS, Gly16 and Gln27 allele frequencies were 62.4% and 57.1% among white and 50.1% and 81.4% among black participants. Over a median follow-up of 11.1 years, 156 and 39 SCD events occurred in white and black participants, respectively. The Gln27Glu variant was associated with SCD risk ( P = 0.008 for general model). SCD risk was higher in Gln27 homozygous participants than in Glu27 carriers ( ethnicity-adjusted hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.17 to 2.09; P = 0.003). The increased risk did not differ significantly between white ( HR, 1.62; 95% CI, 1.18 to 2.23) and black ( HR, 1.23; 95% CI, 0.61 to 2.48) participants, although the confidence interval was wide in blacks. In the CABS replication study, Gln27 homozygous participants similarly had higher SCD risk than Glu27 carriers ( odds ratio, 1.64; 95% CI, 1.02 to 2.63; P = 0.040). Gly16Arg was not associated with SCD risk in either study.Conclusions - Gln27 homozygous individuals have an increased risk of SCD in 2 study populations. Our findings suggest that B2AR plays a role in SCD in humans. Study of genetic variation within the B2AR gene may help identify those at increased SCD risk.