Abstract 17695: SCN5A H558R Polymorphism Counteracts Effects of SCN5A Mutations by Decrease Risk Allele Expression Level

The common SCN5A polymorphism, H558R (c.1673A>G,rs1805124), has been reported to be a genetic modulator of Brugada syndrome (BrS) carrying a SCN5A mutation. H558R has been known to improve the sodium channel activity in mutated channels by restoring the abnormal channel gating kinetics or membrane trafficking. The mechanisms by which H558R rescues the SCN5A mutations remain incompletely defined. We investigated the possible mechanism of why H558R modifies the effects brought by an SCN5A mutation. We investigated rs1805124 in 95 BrS patients (91 males, mean age 42 ± 14 years) and 1,875 normal controls (1546 male, mean age 54±18 years). We obtained the right atrial sections during aortic aneurysm operations from 21 patients and rs1805124 was also genotyped in them. Using cDNA of these patients, we examined the expression level of SCN5A by real time RT-PCR and whether splicing of exon 9 to exon 10 in SCN5A was correct by RT-PCR.and evaluate the difference between the genotypes of rs1805124. Additionally, we ...