title: The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy.
abstract: 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.
authors.affiliation: Molecular Biology Division, Biomedical Research Foundation, Academy of Athens, Athens, Greece.
authors.forename: Demetrios A
authors.initials: DA
authors.lastname: Arvanitis
authors.forename: Despina
authors.initials: D
authors.lastname: Sanoudou
authors.forename: Fotis
authors.initials: F
authors.lastname: Kolokathis
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Vafiadaki
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Papalouka
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Kontrogianni-Konstantopoulos
authors.forename: George N
authors.initials: GN
authors.lastname: Theodorakis
authors.forename: Ioannis A
authors.initials: IA
authors.lastname: Paraskevaidis
authors.forename: Stamatios
authors.initials: S
authors.lastname: Adamopoulos
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Dorn
authors.forename: Dimitrios Th
authors.initials: DT
authors.lastname: Kremastinos
authors.forename: Evangelia G
authors.initials: EG
authors.lastname: Kranias
mesh_terms: 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*
chemical_list: D002135:Calcium-Binding Proteins; C068969:HRC protein, human