Allelic variants of SCN5A and risk of sudden cardiac arrest in patients with coronary artery disease.
BACKGROUND
Most sudden cardiac arrests occur in patients who have associated significant coronary artery disease (CAD), but current methods of risk stratification are inadequate.


OBJECTIVE
The purpose of this study was to evaluate whether allelic variation of SCN5A could determine risk of sudden cardiac arrest among patients with CAD.


METHODS
This case-control study was conducted as part of the ongoing Oregon Sudden Unexpected Death Study (Ore-SUDS). Cases of sudden cardiac arrest with associated CAD were identified among residents of Multnomah County, Oregon (population 660,486). Geographically matched control subjects had significant CAD but no history of cardiac arrest, ventricular arrhythmia, or syncope. DNA was extracted from blood samples, and all 28 exons of SCN5A were screened for allelic variants using denaturing high-performance liquid chromatography. All identified variants were confirmed by direct sequencing.


RESULTS
Sixty-seven cases (mean age 65 +/- 13 years, 18% female) and 91 controls (mean age 66 +/- 12 years, 30% female) were compared. Race was known in 94% of all patients; 92% of case subjects and 89% of control subjects were Caucasian. No patient had clinically manifest familial long QT syndrome. Nonsynonymous nucleotide changes were found in 4% of cases and 1% of controls (P = .31), with one novel mutation (G1291A) identified in one case subject. Synonymous nucleotide changes were found in 27% of cases and 21% of controls (P = .45).


CONCLUSIONS
The overall prevalence of amino acid-altering polymorphisms of the SCN5A gene was relatively low in both groups. Allelic variants of SCN5A did not contribute to risk of sudden cardiac arrest in this primarily Caucasian population with significant CAD.
Stecker
Eric C
EC
Heart Rhythm Research Laboratory, Division of Cardiovascular Medicine, Oregon Health and Science University, Portland, 97239, USA.
Sono
Megan
M
Wallace
Erin
E
Gunson
Karen
K
Jui
Jonathan
J
Chugh
Sumeet S
SS
D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000150:complications / Q000235:genetics*; D005260:Female; D006323:Heart Arrest / Q000209:etiology / Q000235:genetics*; D006801:Humans; D008297:Male; D009124:Muscle Proteins / Q000235:genetics*; D062554:NAV1.5 Voltage-Gated Sodium Channel; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D015222:Sodium Channels / Q000235:genetics*
D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels