Microsatellite polymorphism in the heme oxygenase-1 gene promoter and the risk of atrial fibrillation in Taiwanese

Abstract

Background: Atrial fibrillation (AF) is associated with increased oxidative stress. Emerging evidence suggests that heme oxygenase-1 (HO-1) is a potent antioxidant system against various oxidative stress-related diseases. The human HO-1 promoter has a CT-repeat length polymorphism that can determine the level of gene transcription. Copyright: Objective: The aim of this study is to assess the role of the CT-repeat polymorphism in the promoter region of the HO-1 gene in Chinese-Taiwanese patients with AF. Methods and Results: This study enrolled 200 AF patients and 240 controls, comparable for age and gender. In each subject, the length of CT-repeat polymorphism in the HO-1 promoter region was examined by polymerase chain reactions. The frequencies of long CT-repeat alleles (≥32) were significantly higher in AF patients than in controls. Multivariate analysis showed that the presence of long allele was significantly and independently associated with AF (odds ratio: 1.91, 95% Cl 1.07-3.72; P=0.028). Right atrial tissues from patients with chronic AF were investigated with immunoconfocal microscopy. Patients homo,'gous for shorter CT-repeat alleles exhibited greater HO-1 expression in their atria than those homozygous for longer alleles, which was reflected by less oxidative stress, myofibril degradation, and fibrosis in the atria of patients with shorter CT-repeat. In vitro, transient transfection assay in HL-1 atrial myocytes showed that the responsiveness of HO-1 transcriptional activity to tachypacing was inversely correlated with the length of the CT-repeats. Conclusion:Our results suggest that the HO-1 microsatellite polymorphism may contribute to the genetic background of AF in Chinese-Taiwanese patients.