Abstract 12889: 1291-3 C>A Polymorphism is Linked to H558R Polymorphism: Genetic Modulators of Brugada Syndrome
BACKGROUND: Clinical relevance of SCN5A gene polymorphisms in Brugada syndrome has not yet been completely elucidated. In this study, we investigated the clinical implication of 1291-3 C>A in intron 9 polymorphism on the phenotype of Brugada syndrome.
METHODS: The study population comprised 72 Brugada syndrome subjects (mean age 42 ± 14 years, 68 males and 4 females), which included 20 subjects with a history ventricular fibrillation (VF) and 52 without a history of VF. We measured the PR, QRS, and QTc intervals from leads II and the J-point amplitude from leads V1 and V2 of a 12-lead ECG. We also evaluated signal-averaged ECG and electrophysiological parameters. We checked for SCN5A gene mutations and polymorphisms by resequencing and investigated the implication of 1291-3 C>A in intron 9 polymorphism on the phenotype of Brugada syndrome.
RESULTS: We detected 1291-3 C>A in intron 9 polymorphism in 7 of 72 subjects (9.7%) and H558R polymorphism in 10 of 72 subjects (13.8%); however, no exonic mutation of SCN5A was detected in any subject. 1291-3 C>A in intron 9 and H558R polymorphisms existed concurrently, except in one subject, suggesting that both polymorphisms were linked to each other. One subject with only H558R polymorphism and without 1291-3 C>A had a VF episode after implanted cardioverter defibrillator, while the others were asymptomatic.The 1291-3 C>A carriers had a lower J-point elevation in lead V1 compared with noncarriers (1.4 ± 0.1 vs 2.7 ± 0.4 mv, P < 0.05). Other 12-lead ECG, signal-averaged ECG, and electrophysiological parameters were similar in subjects with and without 1291-3 C>A in intron 9 polymorphism.
CONCLUSION: H558R polymorphism has been reported as a modulator of Brugada syndrome. We demonstrated that 1291-3 C>A in intron 9 and H558R polymorphisms were essentially linked to each other and that 1291-3 C>A in intron 9 polymorphism was a stronger protective genetic modulator of Brugada syndrome than H558R.
- © 2012 by American Heart Association, Inc.