Common SCN10A variants modulate PR interval and heart rate response during atrial fibrillation.

Delaney JT, Muhammad R, Shi Y, Schildcrout JS, Blair M, Short L, Roden DM, Darbar D
Europace. 2014 16 (4): 485-90

PMID: 24072447 · PMCID: PMC3977588 · DOI:10.1093/europace/eut278

AIMS - 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.

METHODS AND 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.

CONCLUSION - 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.

MeSH Terms (20)

Action Potentials Aged Atrial Fibrillation Electrocardiography Female Genetic Predisposition to Disease Heart Conduction System Heart Rate Humans Male Middle Aged NAV1.8 Voltage-Gated Sodium Channel Phenotype Polymorphism, Single Nucleotide Prospective Studies Registries Risk Assessment Risk Factors Tennessee Time Factors

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