The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy

Demetrios A. Arvanitis, Despina Sanoudou, Fotis Kolokathis, Elizabeth Vafiadaki, Vasiliki Papalouka, Aikaterini Kontrogianni-Konstantopoulos, George N. Theodorakis, Ioannis A. Paraskevaidis, Stamatios Adamopoulos, Gerald W. Dorn, Dimitrios Th Kremastinos, Evangelia G. Kranias

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)2514-2525
Number of pages12
JournalEuropean Heart Journal
Volume29
Issue number20
DOIs
Publication statusPublished - 1 Oct 2008
Externally publishedYes

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Calcium-Binding Proteins
Dilated Cardiomyopathy
Histidine
Cardiac Arrhythmias
Calcium
Regression Analysis
Amino Acids

Keywords

  • Calcium
  • Defibrillation
  • Prognosis
  • Sarcoplasmic reticulum

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Arvanitis, D. A., Sanoudou, D., Kolokathis, F., Vafiadaki, E., Papalouka, V., Kontrogianni-Konstantopoulos, A., ... Kranias, E. G. (2008). The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy. European Heart Journal, 29(20), 2514-2525. https://doi.org/10.1093/eurheartj/ehn328

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.

In: European Heart Journal, Vol. 29, No. 20, 01.10.2008, p. 2514-2525.

Research output: Contribution to journalArticle

Arvanitis, DA, Sanoudou, D, Kolokathis, F, Vafiadaki, E, Papalouka, V, Kontrogianni-Konstantopoulos, A, Theodorakis, GN, Paraskevaidis, IA, Adamopoulos, S, Dorn, GW, Kremastinos, DT & Kranias, EG 2008, 'The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy', European Heart Journal, vol. 29, no. 20, pp. 2514-2525. https://doi.org/10.1093/eurheartj/ehn328
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. In: European Heart Journal. 2008 ; Vol. 29, No. 20. pp. 2514-2525.
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abstract = "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.",
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T1 - The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy

AU - Arvanitis, Demetrios A.

AU - Sanoudou, Despina

AU - Kolokathis, Fotis

AU - Vafiadaki, Elizabeth

AU - Papalouka, Vasiliki

AU - Kontrogianni-Konstantopoulos, Aikaterini

AU - Theodorakis, George N.

AU - Paraskevaidis, Ioannis A.

AU - Adamopoulos, Stamatios

AU - Dorn, Gerald W.

AU - Kremastinos, Dimitrios Th

AU - Kranias, Evangelia G.

PY - 2008/10/1

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N2 - 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.

AB - 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.

KW - Calcium

KW - Defibrillation

KW - Prognosis

KW - Sarcoplasmic reticulum

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