Microsatellite Polymorphism in Promoter of Heme Oxygenase-1 Gene Is Associated with Susceptibility to Atrial Fibrillation

Atrial fibrillation (AF) is now recognized to be the most common sustained cardiac arrhythmia and a major public health burden. By genetic association study, some genetic variants or polymorphisms related to the mechanism of AF have been found to be associated with common AF. Accumulating evidence suggests that there is a link between oxidative processes and AF. Recently it was showed that the expression of the inducible heme oxygenase-1 (HO-1) isozyme, a marker of tissue oxidative stress, is higher in left atrial sites with stronger structural remodeling in patients affected by chronic AF. We hypothesize that the (GT)n dinucleotide repeat polymorphism in the promoter region of HO-1 gene is associated with AF by modifying atrial remodeling response to oxidative stress. Therefore, we plan to investigate whether: 1. Rapid activation of HL-1 atrial myocytes induces the expression of HO-1. 2. The induction of HO-1 in HL-1 atrial myocytes by rapid pacing is regulated at transcriptional level. 3. HO-1 plays a protective role against rapid pacing-induced electrical and structural remodeling in HL-1 atrial myocytes. 4. HO-1 plays a protective role against rapid pacing-induced oxidative stress in HL-1 atrial myocytes. 5. The level of human HO-1 transcription induced by rapid pacing is determined by the lengh (number) of dinucleotide (GT) repeats in the promoter region of HO-1 gene. 6. Microsatellite (GT-repeat) polymorphism in the HO-1 gene promoter is associated with atrial fibrillation. Hopefully, our study will offer a deeper understanding about oxidative stress-induced cellular structural and electrical remodeling in AF. The results of our study may help define the role of HO-1 in AF and provide a useful target for therapeutic intervention in AF.

Project ID:PC10009-0105
External Project ID:NSC100-2314-B182-049