中国扩张型心肌病患者的心肌肌钙蛋白T（TNNT2）突变

Cardiac troponin T (TNNT2) mutations in chinese dilated cardiomyopathy patients.

作者信息

Li Xiaoping, Luo Rong, Gu Haiyong, Deng Yun, Xu Xiaolei, Wu Xiushan, Hua Wei

机构信息

Cardiac Arrhythmia Center, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100037, China ; Department of Cardiology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China.

The Center of Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Science, Hunan Normal University, Changsha, Hunan 410081, China.

出版信息

Biomed Res Int. 2014;2014:907360. doi: 10.1155/2014/907360. Epub 2014 Jul 7.

DOI:10.1155/2014/907360

PMID:25110706

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4109665/

Abstract

BACKGROUND

Dilated cardiomyopathy (DCM) is one of the leading causes of heart failure with high morbidity and mortality. Although more than 40 genes have been reported to cause DCM, the role of genetic testing in clinical practice is not well defined. Mutations in the troponin T (TNNT2) gene represent an important subset of known disease-causing mutations associated with DCM. Therefore, the aim of the present study was to determine the genetic variations in TNNT2 and the associations of those variations with DCM in Chinese patients.

METHODS

An approximately 4 kb fragment of the TNNT2 gene was isolated from 103 DCM patients and 192 healthy controls and was analyzed by DNA sequence analysis for genetic variations.

RESULTS

A total of 6 TNNT2 mutations were identified in 99 patients, including a G321T missense mutation (Leu84Phe) and 5 novel intronic mutations. Alleles of two novel SNPs (c.192 + 353 C>A, OR = 0.095, 95% CI: 0.013-0.714, P = 0.022; c.192 + 463 G>A, OR = 0.090, 95% CI: 0.012-0.675, P = 0.019) and SNP rs3729843 (OR = 1.889, 95% CI: 1.252-2.852; P = 0.002) were significantly correlated with DCM.

CONCLUSIONS

These results suggest that the missense mutation (Leu84Phe) and two novel SNPs (c.192 + 353 C>A, c.192 + 463 G>A) in TNNT2 gene might be associated with DCM in the Chinese population.

摘要

背景

扩张型心肌病（DCM）是导致心力衰竭的主要原因之一，发病率和死亡率很高。尽管已有40多个基因被报道可导致DCM，但基因检测在临床实践中的作用尚未明确界定。肌钙蛋白T（TNNT2）基因突变是已知与DCM相关的致病突变的重要子集。因此，本研究的目的是确定中国患者中TNNT2基因的遗传变异及其与DCM的关联。

方法

从103例DCM患者和192例健康对照中分离出约4kb的TNNT2基因片段，并通过DNA序列分析检测遗传变异。

结果

在99例患者中总共鉴定出6个TNNT2突变，包括一个G321T错义突变（Leu84Phe）和5个新的内含子突变。两个新的单核苷酸多态性（SNP）（c.192 + 353 C>A，比值比[OR]=0.095，95%置信区间[CI]：0.013 - 0.714，P = 0.022；c.192 + 463 G>A，OR = 0.090，95% CI：0.012 - 0.675，P = 0.019）以及SNP rs3729843（OR = 1.889，95% CI：1.252 - 2.852；P = 0.002）与DCM显著相关。