TY - JOUR
T1 - Association of CASQ2 polymorphisms with sudden cardiac arrest and heart failure in patients with coronary artery disease
AU - Refaat, Marwan M.
AU - Aouizerat, Bradley E.
AU - Pullinger, Clive R.
AU - Malloy, Mary
AU - Kane, John
AU - Tseng, Zian H.
N1 - Funding Information:
This work was supported in part by the 2011-2012 Heart Rhythm Society Kenneth M. Rosen Fellowship Award in Cardiac Pacing and Electrophysiology to Dr. Refaat and by Grant 5R01 HL102090 from the National Heart, Lung, and Blood Institute to Dr. Tseng.
PY - 2014/4
Y1 - 2014/4
N2 - 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. Conclusion: 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.
AB - 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. Conclusion: 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.
KW - Calsequestrin 2
KW - Congestive heart failure
KW - Coronary artery disease
KW - Genetics
KW - Sudden cardiac arrest
KW - Ventricular arrhythmias
KW - Ventricular tachycardia
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U2 - 10.1016/j.hrthm.2014.01.015
DO - 10.1016/j.hrthm.2014.01.015
M3 - Article
C2 - 24444446
AN - SCOPUS:84896953736
SN - 1547-5271
VL - 11
SP - 646
EP - 652
JO - Heart Rhythm
JF - Heart Rhythm
IS - 4
ER -