1. The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy
- Author
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Vasiliki Papalouka, Dimitrios Th. Kremastinos, Demetrios A. Arvanitis, Stamatios Adamopoulos, Aikaterini Kontrogianni-Konstantopoulos, Gerald W. Dorn, Ioannis Paraskevaidis, Fotis Kolokathis, Despina Sanoudou, Evangelia G. Kranias, Elizabeth Vafiadaki, and George N. Theodorakis
- Subjects
Adult ,Cardiomyopathy, Dilated ,Male ,medicine.medical_specialty ,Genotype ,Heart disease ,Sarcoplasmic reticulum ,Defibrillation ,Clinical Research ,Polymorphism (computer science) ,Internal medicine ,Calcium-binding protein ,Idiopathic dilated cardiomyopathy ,medicine ,Humans ,cardiovascular diseases ,Polymorphism, Genetic ,Proportional hazards model ,business.industry ,Calcium-Binding Proteins ,Heart Failure/Cardiomyopathy ,Arrhythmias, Cardiac ,Dilated cardiomyopathy ,Middle Aged ,Prognosis ,medicine.disease ,Myocardial Contraction ,Defibrillators, Implantable ,Death, Sudden, Cardiac ,Endocrinology ,Circulatory system ,Disease Progression ,cardiovascular system ,Female ,Calcium ,Cardiology and Cardiovascular Medicine ,business - 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.
- Published
- 2008
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