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

Lung An Hsu, Yung Hsin Yeh, Chi-Tai Kuo, Ying Hwa Chen*, Gwo Jyh Chang, Feng Chun Tsai, Wei Jan Chen

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

8 Scopus citations

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.

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.

Original languageEnglish
Article numbere108773
JournalPLoS ONE
Volume9
Issue number9
DOIs
StatePublished - 30 09 2014

Bibliographical note

Publisher Copyright:
© 2014 Hsu et al.

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