β3-AR基因T190C多态性与卡维地洛治疗心力衰竭疗效的相关性  

Association of T190C polymorphism of β3 adrenergic receptor gene with response to carvedilol in patients with chronic heart failure

作　　者：俞海峰[1] 韦凡平[1] 钱国权[1] 李丽芳[1] 张川[1] 程震锋[1] 

机构地区：[1]浙江省湖州市中心医院心内科,313000

出　　处：《中华医学遗传学杂志》2015年第1期101-104,共4页Chinese Journal of Medical Genetics

基　　金：湖州市科技局一般项目（2010YSl9）

摘　　要：目的研究β3肾上腺素能受体（β73adrenergicreceptor，β3-AR）基因T190C多态性与心力衰竭患者基因型的相关性，以及不同基因型患者对卡维地洛治疗心衰的疗效评价。方法330例心力衰竭患者，在接受基础治疗基础上给予最大耐受剂量卡维地洛治疗5个月，治疗前后测定各项指标，包括心率、血压、左心房内径、左心室舒张末期内径、左心室收缩末期内径、左心室射血分数、脑利钠肽及6min行走距离，并作β3-AR基因T190C多态性测定，观察治疗前后各基因型患者指标变化的组间差异。另随机选取300名正常健康人群，进行β3-AR基因T190C多态性测定，比较心力衰竭患者组和健康人群组之间基因型的差异有无统计学意义。结果β3-AR基因T190C位点的等位基因和基因型频率均符合Hardy-Weinberg平衡。位点的基因型及等位基因频率在心力衰竭组和对照组中差异无统计学意义，β3-AR基因T190C多态含TT基因型心力衰竭患者经过卡维地洛疗后左心室射血分数、脑利钠钛较CC基因型患者显著改善。结论β3-AR基因T190C位点的基因型与心力衰竭无明显相关，β3-AR基因T190C多态含T等位基因心力衰竭患者对卡维地洛疗效好于含C等位基因患者。Objective To assess the association of T190C polymorphism of β3 adrenergic receptor gene （β3-AR）with chronic heart failure （CHF）, and to evaluate the effect of this polymorphism on clinical response toβ-AR blockade among patients with CHF. Methods Three hundred and thirty patients with stable CHF receiving basic therapy for heart failure were included. Before initiation and 5 months after the maximal tolerated dose of carvedilol was reached, all indices including heart rate （HR）, blood pressure （BP）, left atrial diameter （LAD）, left ventricular end-diastolic diameter （LVEDD , left ventricular end- systolic diameter （LVESD）, left ventricular ejection fraction （LVEF）, brain natrmretic peptide （BNP） level, 6 rain walk distance were measured and compared with the indices of those with a T190C genotype. Distribution of the T190C polymorphisms in the control group and CHF group was compared. Results The frequencies of T190C genotypes of the β3-AR gene have fit with the Hardy-Weinberg equilibrium. No significant difference was found between the frequencies of T190C alleles and genotypes between the two groups （P〉0.05）. Compared with CC-homozygotes, TT-homozygous patients showed substantially greater improvement in LVEF and BNP （all P〉 0. 01）. Conclusion No difference has been detected in the prevalence of the three genotypes between healthy and CHF subjects. The T190C variation of the β3-AR gene was not associated with increased risk for CHF. CHF patients with a T allele have greater response to carvedilol than those carrying a C allele in ethnic Han Chinese.

关 键 词：心力衰竭 卡维地络 单核苷酸多态性 Β3肾上腺素能受体 

分 类 号：R541[医药卫生—心血管疾病]