Common SCN10A variants modulate PR interval and heart rate response during atrial fibrillation.
OBJECTIVE
SCN10A encodes the sodium channel Nav1.8 implicated by genome-wide association studies as a modulator of atrioventricular conduction (PR interval). In a cohort of patients with atrial fibrillation (AF), we examined whether there was an association between common variants in SCN10A and both the PR interval during normal sinus rhythm and the heart rate response during AF.


RESULTS
Patients prospectively enrolled in the Vanderbilt AF registry with electrocardiograms in normal sinus rhythm and/or AF within 1 year of enrollment were genotyped for two common SCN10A variants rs6795970 and rs12632942. Both variants were associated with the PR interval duration in a gene-dose effect on unadjusted analysis; after adjustment for the covariates age, gender, body mass index, hypertension, congestive heart failure, and medication usage, the association remained for rs6795970 only (P = 0.012, partial R(2) = 0.0139). On unadjusted analysis, heart rate response during AF was associated with rs6795970 (P = 0.035, partial R(2) = 0.015), but not with rs12632942 (P = 0.89), and neither association was significant after adjustment for covariates.


CONCLUSIONS
The common variant rs6795970 in SCN10A is associated with the PR interval duration among healthy patients and those with AF. In addition, this single nucleotide polymorphism trended towards an association with heart rate response during AF indicating the importance of this common SCN10A polymorphism as a marker of atrioventricular conduction.
Division of Cardiovascular Medicine, Departments of Medicine, Vanderbilt University School of Medicine, 2215B Garland Avenue, Room 1275 MRB IV, Room 1275 MRB IV, Nashville, TN 37232-6602, USA.
Jessica T
JT
Delaney
Raafia
R
Muhammad
Yaping
Y
Shi
Jonathan S
JS
Schildcrout
Marcia
M
Blair
Laura
L
Short
Dan M
DM
Roden
Dawood
D
Darbar
D000200:Action Potentials; D000368:Aged; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D004562:Electrocardiography; D005260:Female; D020022:Genetic Predisposition to Disease; D006329:Heart Conduction System / Q000503:physiopathology*; D006339:Heart Rate / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D062559:NAV1.8 Voltage-Gated Sodium Channel / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D013714:Tennessee; D013997:Time Factors
D062559:NAV1.8 Voltage-Gated Sodium Channel; C568317:SCN10A protein, human
Atrial fibrillation; PR interval; SCN10A