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.