Common RyR2 variants associate with ventricular arrhythmias and sudden cardiac death in chronic heart failure.
Ca2+ cycling plays a critical role in heart failure and lethal arrhythmias. As susceptibility to sudden cardiac death is considered to be a heritable trait in general population, we have therefore investigated whether potentially functional variants of genes encoding RyR2 (ryanodine receptor 2) and the L-type Ca2+ channel are related to the risk of ventricular arrhythmias and sudden cardiac death in CHF (chronic heart failure) in a case-control study. We found that the A allele of rs3766871 in RYR2 was associated with an increased risk of ventricular arrhythmias in patients with CHF {odds ratio, 1.66 [95% CI (confidence interval), 1.21-2.26]; P=0.002}. During a median follow-up period of 32 months in 1058 (85.0%) patients, 296 (28.0%) patients died from heart failure, of whom 141 (47.6%) had sudden cardiac death. After adjustment for age, gender and suspected risk factors, patients carrying the A allele of rs3766871 had an increased risk of cardiac death {HR (hazard ratio), 1.53 [95% CI, 1.11-2.12]; P=0.010} and sudden cardiac death [HR, 1.92 (95% CI, 1.25-2.94); P=0.003]. Patients carrying the A allele of rs790896 in RYR2 had a reduced risk of sudden cardiac death [HR, 0.65 (95% CI, 0.45-0.92); P=0.015]. In conclusion, the A allele of rs3766871 in RYR2 not only associates with ventricular arrhythmias, but also serves as an independent predictor of sudden cardiac death, and the A allele of rs790896 in RYR2 is a protective factor against sudden cardiac death in patients with CHF.
Ran
Yuqin
Y
Center for Arrhythmia Diagnosis and Treatment, Fu Wai Cardiovascular Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100037, China.
Chen
Jingzhou
J
Li
Ning
N
Zhang
Weili
W
Feng
Li
L
Wang
Rongrong
R
Hui
Rutai
R
Zhang
Shu
S
Pu
Jielin
J
D000328:Adult; D000368:Aged; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000235:genetics*; D001483:Base Sequence; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D004812:Epidemiologic Methods; D005260:Female; D020022:Genetic Predisposition to Disease; D006333:Heart Failure / Q000150:complications / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*
D019837:Ryanodine Receptor Calcium Release Channel