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

Li X, Luo R, Gu H, Deng Y, Xu X, Wu X, Hua W - Biomed Res Int (2014)

Bottom Line: Mutations in the troponin T (TNNT2) gene represent an important subset of known disease-causing mutations associated with DCM.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.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

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.

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Related in: MedlinePlus

Sequences of TNNT2. Six novel variants in TNNT2 gene in DCM patients, including a missense mutation (G12026T, c.252 G>T, Leu84Phe), five novel variants in introns, respectively.
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fig1: Sequences of TNNT2. Six novel variants in TNNT2 gene in DCM patients, including a missense mutation (G12026T, c.252 G>T, Leu84Phe), five novel variants in introns, respectively.

Mentions: The screening of the 3992-nucleotide fragment of TNNT2 led to the identification of one novel missense mutation. A single-nucleotide variant consisting of a G>T transversion (TTG>TTT) at nucleotide 12026 (G12026T, c.252 G>T) (Figure 1) in exon 9 was found in one DCM patient and would substitute a phenylalanine for the normal leucine at residue 84 (Leu84Phe). This patient was diagnosed at the age of 43 and was clinically symptomatic of heart failure, with LV 60 mm and LV ejection fraction 31%. Additionally, this patient had a familial history of coronary heart disease. In addition, we also identified 5 mutations in introns 6, 7, 9, and 10 in a subset of the DCM patients (Figure 1). Their clinical data are shown in Table 2.


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

Li X, Luo R, Gu H, Deng Y, Xu X, Wu X, Hua W - Biomed Res Int (2014)

Sequences of TNNT2. Six novel variants in TNNT2 gene in DCM patients, including a missense mutation (G12026T, c.252 G>T, Leu84Phe), five novel variants in introns, respectively.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4109665&req=5

fig1: Sequences of TNNT2. Six novel variants in TNNT2 gene in DCM patients, including a missense mutation (G12026T, c.252 G>T, Leu84Phe), five novel variants in introns, respectively.
Mentions: The screening of the 3992-nucleotide fragment of TNNT2 led to the identification of one novel missense mutation. A single-nucleotide variant consisting of a G>T transversion (TTG>TTT) at nucleotide 12026 (G12026T, c.252 G>T) (Figure 1) in exon 9 was found in one DCM patient and would substitute a phenylalanine for the normal leucine at residue 84 (Leu84Phe). This patient was diagnosed at the age of 43 and was clinically symptomatic of heart failure, with LV 60 mm and LV ejection fraction 31%. Additionally, this patient had a familial history of coronary heart disease. In addition, we also identified 5 mutations in introns 6, 7, 9, and 10 in a subset of the DCM patients (Figure 1). Their clinical data are shown in Table 2.

Bottom Line: Mutations in the troponin T (TNNT2) gene represent an important subset of known disease-causing mutations associated with DCM.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.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

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.

Show MeSH
Related in: MedlinePlus