Background: Brugada syndrome predisposes some subjects to ventricular tachyarrhythmias and sudden cardiac death. Mutations in SCN5A gene have been associated with approximately 25% of Brugada syndrome patients. A common variant in SCN5A, H558R has shown to improve sodium channel activity in mutated channels. We studied whether common variant H558R has any clinical implications in the phenotype of Brugada syndrome.
Methods: Our study population consisted of Brugada syndrome subjects 75 with SCN5A mutation and 92 without SCN5A mutation. Their mean age was 39 +/- 15 and 42 +/- 17 years, and 65% and 86% were male, respectively. We measured PR-, QRS-, QTc-intervals from leads II and V2 of the 12-lead ECG. We also evaluated J-point amplitude from lead V2 and R'/S ratio from lead aVR (the "aVR sign"). The H558R (A-->G) genotype was detected with direct sequencing of the SCN5A gene.
Results: The AA genotype carriers had longer QRS duration in lead II (P = 0.017) and higher J-point elevation in lead V2 (P = 0.013), higher "aVR sign" (P = 0.005) and a trend toward more subjects with symptoms (P = 0.067) than G allele carriers. None of the results were significant in Brugada syndrome subjects without SCN5A mutation.
Conclusion: The common variant H558R seems to be a genetic modulator of Brugada syndrome among carriers of a SCN5A mutation, in whom the presence of the less common allele G improves the ECG characteristics and clinical phenotype.