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The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy
AIMS: To investigate whether genetic variants of the histidine-rich calcium (HRC)-binding protein are associated with idiopathic dilated cardiomyopathy (DCM) and its progression. METHODS AND RESULTS: We screened 123 idiopathic DCM patients and 96 healthy individuals by single-strand conformation pol...
Autores principales: | , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2567024/ https://www.ncbi.nlm.nih.gov/pubmed/18617481 http://dx.doi.org/10.1093/eurheartj/ehn328 |
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author | Arvanitis, Demetrios A. Sanoudou, Despina Kolokathis, Fotis Vafiadaki, Elizabeth Papalouka, Vasiliki Kontrogianni-Konstantopoulos, Aikaterini Theodorakis, George N. Paraskevaidis, Ioannis A. Adamopoulos, Stamatios Dorn, Gerald W. Kremastinos, Dimitrios Th. Kranias, Evangelia G. |
author_facet | Arvanitis, Demetrios A. Sanoudou, Despina Kolokathis, Fotis Vafiadaki, Elizabeth Papalouka, Vasiliki Kontrogianni-Konstantopoulos, Aikaterini Theodorakis, George N. Paraskevaidis, Ioannis A. Adamopoulos, Stamatios Dorn, Gerald W. Kremastinos, Dimitrios Th. Kranias, Evangelia G. |
author_sort | Arvanitis, Demetrios A. |
collection | PubMed |
description | AIMS: To investigate whether genetic variants of the histidine-rich calcium (HRC)-binding protein are associated with idiopathic dilated cardiomyopathy (DCM) and its progression. METHODS AND RESULTS: We screened 123 idiopathic DCM patients and 96 healthy individuals by single-strand conformation polymorphism analysis and direct sequencing for genetic variants in HRC. Six polymorphisms were detected: Leu35Leu (A/G), Ser43Asn (G/A), Ser96Ala (T/G), Glu202_Glu203insGlu (−/GAG), Asp261del (GAT/−), and an in-frame insertion of 51 amino acids at His321. The analysis of their frequencies did not reveal any significant correlation with DCM development. However, the Ser96Ala polymorphism exhibited a statistically significant correlation with the occurrence of life-threatening ventricular arrhythmias. During a follow-up of 4.02 ± 2.4 years, the risk for ventricular arrhythmias was higher (HR, 9.620; 95% CI, 2.183–42.394; P = 0.003) in the Ala/Ala patients, compared with Ser/Ser homozygous patients. On multivariable Cox regression analysis, the Ser96Ala polymorphism was the only significant genetic arrythmogenesis predictor in DCM patients (HR, 4.191; 95% CI, 0.838–20.967; P = 0.018). CONCLUSION: The Ser96Ala genetic variant of HRC is associated with life-threatening ventricular arrhythmias in idiopathic DCM and may serve as an independent predictor of susceptibility to arrhythmogenesis in the setting of DCM. |
format | Text |
id | pubmed-2567024 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-25670242009-02-25 The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy Arvanitis, Demetrios A. Sanoudou, Despina Kolokathis, Fotis Vafiadaki, Elizabeth Papalouka, Vasiliki Kontrogianni-Konstantopoulos, Aikaterini Theodorakis, George N. Paraskevaidis, Ioannis A. Adamopoulos, Stamatios Dorn, Gerald W. Kremastinos, Dimitrios Th. Kranias, Evangelia G. Eur Heart J Clinical Research AIMS: To investigate whether genetic variants of the histidine-rich calcium (HRC)-binding protein are associated with idiopathic dilated cardiomyopathy (DCM) and its progression. METHODS AND RESULTS: We screened 123 idiopathic DCM patients and 96 healthy individuals by single-strand conformation polymorphism analysis and direct sequencing for genetic variants in HRC. Six polymorphisms were detected: Leu35Leu (A/G), Ser43Asn (G/A), Ser96Ala (T/G), Glu202_Glu203insGlu (−/GAG), Asp261del (GAT/−), and an in-frame insertion of 51 amino acids at His321. The analysis of their frequencies did not reveal any significant correlation with DCM development. However, the Ser96Ala polymorphism exhibited a statistically significant correlation with the occurrence of life-threatening ventricular arrhythmias. During a follow-up of 4.02 ± 2.4 years, the risk for ventricular arrhythmias was higher (HR, 9.620; 95% CI, 2.183–42.394; P = 0.003) in the Ala/Ala patients, compared with Ser/Ser homozygous patients. On multivariable Cox regression analysis, the Ser96Ala polymorphism was the only significant genetic arrythmogenesis predictor in DCM patients (HR, 4.191; 95% CI, 0.838–20.967; P = 0.018). CONCLUSION: The Ser96Ala genetic variant of HRC is associated with life-threatening ventricular arrhythmias in idiopathic DCM and may serve as an independent predictor of susceptibility to arrhythmogenesis in the setting of DCM. Oxford University Press 2008-10 2008-07-09 /pmc/articles/PMC2567024/ /pubmed/18617481 http://dx.doi.org/10.1093/eurheartj/ehn328 Text en Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org |
spellingShingle | Clinical Research Arvanitis, Demetrios A. Sanoudou, Despina Kolokathis, Fotis Vafiadaki, Elizabeth Papalouka, Vasiliki Kontrogianni-Konstantopoulos, Aikaterini Theodorakis, George N. Paraskevaidis, Ioannis A. Adamopoulos, Stamatios Dorn, Gerald W. Kremastinos, Dimitrios Th. Kranias, Evangelia G. The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy |
title | The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy |
title_full | The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy |
title_fullStr | The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy |
title_full_unstemmed | The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy |
title_short | The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy |
title_sort | ser96ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy |
topic | Clinical Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2567024/ https://www.ncbi.nlm.nih.gov/pubmed/18617481 http://dx.doi.org/10.1093/eurheartj/ehn328 |
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