Abstract 12728: Common Variant Near Hey2 as a Protective Modifier of Ventricular Fibrillation in Brugada Syndrome by Modurating QTc Interval

Abstract

Introduction: A recent genome-wide association study (GWAS) identified that three loci, SCN10A (rs10428132), SCN5A (rs11708996), and one downstream from HEY2 gene (rs9388451) were associated with Brugada syndrome. Methods: We investigated these 3 single nucleotide polymorphisms (SNPs) in 94 Japanese patients diagnosed with Brugada syndrome and 1,978 healthy controls. Results: Both rs10428132 at SCN10A and rs9388451near HEY2 were associated with Brugada syndrome [ P = 6.13 х 10 –14 ;odds ratio (OR), 8.0 and P = 8.0 х 10 –4 ; OR, 2.5, respectively). However, the C HEY2 allele was more frequent in Brugada syndrome patients without ventricular fibrillation (VF) than those with VF (53.7% vs. 40%, P = 0.04). This suggests a protective effect of this allele against VF occurrence, which may conflict with previous GWAS findings. The QTc interval was significantly longer in patients with the HEY2 risk allele than those without it (CC: 422 ± 3.8 vs. CT: 409 ± 4.8 vs. TT: 381 ± 9.5 ms, P = 0.0004). The other electrocardiogram parameters were unrelated to the HEY2 allele. PQ interval was longer in patients with the SCN10A risk allele than those without it (CC: 157 ± 2.5 vs. CT: 172 ± 5.3 vs. TT: 172 ± 3.5 ms, P = 0.0019), but the SCN10A SNP was not associated with clinical severity of Brugada syndrome. Conclusions: These results suggest that the HEY2 SNP may be a prognostic marker for Brugada syndrome, protecting VF occurrence presumably by regulating repolarization current.