Microsatellite Polymorphism in the Heme Oxygenase-1 Gene Promoter and the Risk of Atrial Fibrillation in Taiwanese

نویسندگان

  • Lung-An Hsu
  • Yung-Hsin Yeh
  • Chi-Tai Kuo
  • Ying-Hwa Chen
  • Gwo-Jyh Chang
  • Feng-Chun Tsai
  • Wei-Jan Chen
  • Yiru Guo
چکیده

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 GT-repeat length polymorphism that can determine the level of gene transcription. OBJECTIVE The aim of this study is to assess the role of the GT-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 GT-repeat polymorphism in the HO-1 promoter region was examined by polymerase chain reactions. The frequencies of long GT-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% CI 1.07-3.72; P = 0.028). Right atrial tissues from patients with chronic AF were investigated with immunoconfocal microscopy. Patients homozygous for shorter GT-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 GT-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 GT-repeats. CONCLUSION Our results suggest that the HO-1 microsatellite polymorphism may contribute to the genetic background of AF in Chinese-Taiwanese patients.

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عنوان ژورنال:

دوره 9  شماره 

صفحات  -

تاریخ انتشار 2014