The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy.
OBJECTIVE
To investigate whether genetic variants of the histidine-rich calcium (HRC)-binding protein are associated with idiopathic dilated cardiomyopathy (DCM) and its progression.


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).


CONCLUSIONS
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.
Arvanitis
Demetrios A
DA
Molecular Biology Division, Biomedical Research Foundation, Academy of Athens, Athens, Greece.
Sanoudou
Despina
D
Kolokathis
Fotis
F
Vafiadaki
Elizabeth
E
Papalouka
Vasiliki
V
Kontrogianni-Konstantopoulos
Aikaterini
A
Theodorakis
George N
GN
Paraskevaidis
Ioannis A
IA
Adamopoulos
Stamatios
S
Dorn
Gerald W
GW
Kremastinos
Dimitrios Th
DT
Kranias
Evangelia G
EG
D000328:Adult; D001145:Arrhythmias, Cardiac / Q000235:genetics*; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000503:physiopathology; D016757:Death, Sudden, Cardiac / Q000517:prevention & control; D017147:Defibrillators, Implantable; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000502:physiology; D011110:Polymorphism, Genetic / Q000235:genetics*
D002135:Calcium-Binding Proteins; C068969:HRC protein, human