肌联蛋白截断变异增加肥厚型心肌病患者心血管死亡风险。

Titin-Truncating Variants Increase the Risk of Cardiovascular Death in Patients With Hypertrophic Cardiomyopathy.

机构信息

State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Department of Cardiovascular Disease, Mayo Clinic, Rochester, Minnesota, USA; Department of Medical Ultrasonics, the Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China.

出版信息

Can J Cardiol. 2017 Oct;33(10):1292-1297. doi: 10.1016/j.cjca.2017.05.020. Epub 2017 Jun 8.

DOI:10.1016/j.cjca.2017.05.020

PMID:28822653

Abstract

BACKGROUND

Titin-truncating variants (TTNtv) have been detected in a variety of cardiomyopathies and represent the most common cause of dilated cardiomyopathy. However, their significance in hypertrophic cardiomyopathy (HCM) is still unclear.

METHODS

The titin gene (TTN) was sequenced for truncating variants in a cohort of 529 Chinese patients with HCM and 307 healthy controls. Baseline and follow-up clinical data (for 4.7 ± 3.2 years) from these patients were obtained.

RESULTS

We identified 13 and 8 TTNtv in patients with HCM (13 of 529 [2.5%]) and controls (8 of 307 [2.6%]), respectively. The prevalence of TTNtv in patients with HCM and in healthy controls was comparable (P = 0.895). There were no significant differences in baseline characteristics between patients with and those without TTNtv. However, during follow-up, patients with TTNtv (3 of 13 [23.1%]) were more likely to experience cardiovascular death compared with those without TTNtv (39 of 516 [7.6%]) [adjusted hazard ratio, 6.88; 95% confidence interval, 2.04-23.20; P = 0.002).

CONCLUSIONS

Our study suggests that TTNtv might be a genetic modifier of HCM and confer an increased risk for cardiovascular death.

摘要

背景

肌联蛋白截断变异（TTNtv）已在多种心肌病中被检测到，是扩张型心肌病的最常见病因。然而，其在肥厚型心肌病（HCM）中的意义仍不清楚。

方法

对 529 例中国 HCM 患者和 307 例健康对照者的肌联蛋白基因（TTN）进行截断变异测序。获取这些患者的基线和随访临床数据（随访时间为 4.7±3.2 年）。

结果

我们在 HCM 患者（13 of 529 [2.5%]）和对照组（8 of 307 [2.6%]）中分别发现了 13 例和 8 例 TTNtv。HCM 患者和健康对照者 TTNtv 的患病率相似（P=0.895）。有 TTNtv 的患者和无 TTNtv 的患者在基线特征方面无显著差异。然而，在随访期间，有 TTNtv 的患者（13 例中的 3 例[23.1%]）发生心血管死亡的风险高于无 TTNtv 的患者（516 例中的 39 例[7.6%]）[校正后的危险比，6.88；95%置信区间，2.04-23.20；P=0.002]。