Takotsubo心肌病(中医),也被称为“心碎综合症”是一种心力衰竭,其特征是在没有阻塞性冠状动脉病变的情况下短暂的心室功能障碍。尽管与儿茶酚胺水平升高有关,病理生理机制未知。复发和家族遗传力表明遗传倾向。一些小型研究已经调查了三个不同基因座之间的关联;β1-肾上腺素受体(ADRB1),G蛋白偶联受体激酶5(GRK5),Bcl相关基因基因3(BAG3)与中医,但尚未达成共识。
使用瑞典冠状动脉造影和血管成形术注册(SCAAR)招募参与者。确定了没有冠心病(CAD)的中医患者(n=258),并选择了年龄和性别匹配的(n=164)和没有(n=243)CAD的受试者作为对照。从唾液中分离DNA,并对ADRB1,GRK5和BAG3基因中的候选单核苷酸多态性进行基因分型。比较了所研究多态性的等位基因频率和几率比(OR)和95%置信区间(CI)。分别为中医患者和对照组计算。
中医患者和对照组的等位基因频率没有差异。使用对照作为参考,具有至少一个次要等位基因的TCM患者的OR(CI)为ADRB1的1.07(0.75-1.55),GRK5的0.45(0.11-1.85)和BAG3的1.27(0.74-2.19)。
通过对一个大的takotsubo队列进行基因分型,我们证明了ADRB1,GRK5和BAG3基因中候选SNP之间缺乏关联,早先建议为中医作出贡献。我们的结果表明,需要扩大对有助于中医的新遗传候选者的搜索。
Takotsubo cardiomyopathy (TCM), also known as \"broken heart syndrome\", is a type of heart failure characterized by transient ventricular dysfunction in the absence of obstructive coronary lesions. Although associated with increased levels of catecholamines, pathophysiological mechanisms are unknown. Relapses and family heritability indicate a genetic predisposition. Several small studies have investigated associations between three different loci; the β1-adrenic receptor (ADRB1), G-protein-coupled receptor kinase 5 (GRK5), Bcl-associated athanogene 3 (BAG3) and TCM but no consensus has been reached.
Participants were recruited using the Swedish Coronary Angiography and Angioplasty Register (SCAAR). TCM patients without coronary artery disease (CAD)(n = 258) were identified and age- and sex-matched subjects with (n = 164) and without (n = 243) CAD were selected as controls. DNA was isolated from saliva and genotyped for candidate single nucleotide polymorphisms in the ADRB1, GRK5 and BAG3 genes. Allele frequencies and Odds Ratios (OR) with 95% Confidence Intervals (CI) for the investigated polymorphisms were compared, respectively calculated for TCM patients and controls.
There were no differences in allele frequencies between TCM patients and controls. OR (CI) for TCM patients having at least one minor allele using controls as reference were 1.07 (0.75-1.55) for ADRB1, 0.45 (0.11-1.85) for GRK5 and 1.27 (0.74-2.19) for BAG3.
By genotyping a large takotsubo cohort, we demonstrate a lack of association between candidate SNPs in the ADRB1, GRK5 and BAG3 genes, earlier suggested to contribute to TCM. Our result indicates a need to expand the search for new genetic candidates contributing to TCM.