Association of CASQ2 polymorphisms with sudden cardiac arrest and heart failure in patients with coronary artery disease.
BACKGROUND
Abnormal calcium handling plays a crucial role in arrhythmias, sudden cardiac arrest (SCA), and congestive heart failure (CHF). Calsequestrin 2 (CASQ2) mutations affect calcium release and initiate malignant ventricular arrhythmias (VAs) and SCA syndromes. Common single nucleotide polymorphisms (SNPs) in CASQ2 may be associated with SCA in patients with coronary artery disease (CAD).


OBJECTIVE
The purpose of this study was to examine the association of common CASQ2 SNPs with the risk of SCA in patients with CAD.


METHODS
CASQ2 SNPs (n = 14) were genotyped and analyzed in a case control study comparing 114 patients with CAD and SCA due to VA to 311 CAD controls without VA or SCA.


RESULTS
Multivariate logistic regression adjusting for age and CHF status identified an association between rs7521023 with SCA (odds ratio [OR] 2.72, 95% confidence interval [CI] 1.44-5.13, P = .002). The substantial impact of CHF on SCA in the model (OR 26.6, 95% CI 13.40-52.70, P <.001) led us to further examine the relationship between CHF, SCA, and CASQ2 SNPs. We identified 2 CASQ2 variants (rs7521023: OR 0.4, 95% CI 0.25-0.76, P = .003; rs6684209: OR 19.8, 95% CI 3.63-108.2, P <.001) associated with CHF after adjusting for SCA, age, gender, and hypertension.


CONCLUSIONS
We observed association between a CASQ2 polymorphism and SCA due to VA in patients with CAD adjusting for CHF and independent associations between CASQ2 SNPs and CHF adjusting for SCA. Further investigation in independent cohorts is needed to confirm these findings.
Department of Internal Medicine, Cardiovascular Medicine/Cardiac Electrophysiology, American University of Beirut Faculty of Medicine, Beirut, Lebanon.
Marwan M
MM
Refaat
Department of Physiologic Nursing; Institute for Human Genetics.
Bradley E
BE
Aouizerat
Cardiovascular Research Institute, University of California, San Francisco, California.
Clive R
CR
Pullinger
Cardiovascular Research Institute, University of California, San Francisco, California.
Mary
M
Malloy
Cardiovascular Research Institute, University of California, San Francisco, California.
John
J
Kane
Section of Cardiac Electrophysiology, Department of Medicine. Electronic address: zhtseng@medicine.ucsf.edu.
Zian H
ZH
Tseng
D000368:Aged; D001145:Arrhythmias, Cardiac / Q000150:complications; D002155:Calsequestrin / Q000235:genetics*; D003327:Coronary Disease / Q000150:complications*; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D005260:Female; D006333:Heart Failure / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000150:complications; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
C443109:CASQ2 protein, human; D002155:Calsequestrin
Calsequestrin 2; Congestive heart failure; Coronary artery disease; Genetics; Sudden cardiac arrest; Ventricular arrhythmias; Ventricular tachycardia