Dataset Information

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 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.

SUBMITTER: Hsu LA

PROVIDER: S-EPMC4182563 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

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

Hsu Lung-An LA Yeh Yung-Hsin YH Kuo Chi-Tai CT Chen Ying-Hwa YH Chang Gwo-Jyh GJ Tsai Feng-Chun FC Chen Wei-Jan WJ

PloS one 20140930 9

<h4>Background</h4>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.<h4>Objective</h4>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 patient ...[more]

PMID: 25268359

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Project description:BackgroundArsenic is a strong stimulus of heme oxygenase (HO)-1 expression in experimental studies in response to oxidative stress caused by a stimulus. A functional GT-repeat polymorphism in the HO-1 gene promoter was inversely correlated to the development of coronary artery disease in diabetics and development of restenosis following angioplasty in patients. The role of this potential vascular protective factor in carotid atherosclerosis remains unclear. We previously reported a graded association of arsenic exposure in drinking water with an increased risk of carotid atherosclerosis. In this study, we investigated the relationship between HO-1 genetic polymorphism and the risk of atherosclerosis related to arsenic.MethodsThree-hundred and sixty-seven participants with an indication of carotid atherosclerosis and an additional 420 participants without the indication, which served as the controls, from two arsenic exposure areas in Taiwan, a low arsenic-exposed Lanyang cohort and a high arsenic-exposed LMN cohort, were studied. Carotid atherosclerosis was evaluated using a duplex ultrasonographic assessment of the extracranial carotid arteries. Allelic variants of (GT)n repeats in the 5'-flanking region of the HO-1 gene were identified and grouped into a short (S) allele (< 27 repeats) and long (L) allele (? 27 repeats). The association of atherosclerosis and the HO-1 genetic variants was assessed by a logistic regression analysis, adjusted for cardiovascular risk factors.ResultsAnalysis results showed that arsenic's effect on carotid atherosclerosis differed between carriers of the class S allele (OR 1.39; 95% CI 0.86-2.25; p = 0.181) and non-carriers (OR 2.65; 95% CI 1.03-6.82; p = 0.044) in the high-exposure LMN cohort. At arsenic exposure levels exceeding 750 ?g/L, difference in OR estimates between class S allele carriers and non-carriers was borderline significant (p = 0.051). In contrast, no such results were found in the low-exposure Lanyang cohort.ConclusionsThis exploratory study suggests that at a relatively high level of arsenic exposure, carriers of the short (GT)n allele (< 27 repeats) in the HO-1 gene promoter had a lower probability of developing carotid atherosclerosis than non-carriers of the allele after long-term arsenic exposure via ground water. The short (GT)n repeat in the HO-1 gene promoter may provide protective effects against carotid atherosclerosis in individuals with a high level of arsenic exposure.

Project description:BACKGROUND:Heme oxygenase-1 (HO-1) is a critical cytoprotective enzyme that limits oxidative stress, inflammation, and cellular injury within the central nervous system (CNS) and other tissues. We previously demonstrated that HO-1 protein expression is decreased within the brains of HIV+ subjects and that this HO-1 reduction correlates with CNS immune activation and neurocognitive dysfunction. To define a potential CNS protective role for HO-1 against HIV, we analyzed a well-characterized HIV autopsy cohort for two common HO-1 promoter region polymorphisms that are implicated in regulating HO-1 promoter transcriptional activity, a (GT)n dinucleotide repeat polymorphism and a single nucleotide polymorphism (A(-413)T). Shorter HO-1 (GT)n repeats and the 'A' SNP allele associate with higher HO-1 promoter activity. METHODS:Brain dorsolateral prefrontal cortex tissue samples from an autopsy cohort of HIV-, HIV+, and HIV encephalitis (HIVE) subjects (n = 554) were analyzed as follows: HO-1 (GT)n polymorphism allele lengths were determined by PCR and capillary electrophoresis, A(-413)T SNP alleles were determined by PCR with allele specific probes, and RNA expression of selected neuroimmune markers was analyzed by quantitative PCR. RESULTS:HIV+ subjects with shorter HO-1 (GT)n alleles had a significantly lower risk of HIVE; however, shorter HO-1 (GT)n alleles did not correlate with CNS or peripheral viral loads. In HIV+ subjects without HIVE, shorter HO-1 (GT)n alleles associated significantly with lower expression of brain type I interferon response markers (MX1, ISG15, and IRF1) and T-lymphocyte activation markers (CD38 and GZMB). No significant correlations were found between the HO-1 (GT)n repeat length and brain expression of macrophage markers (CD163, CD68), endothelial markers (PECAM1, VWF), the T-lymphocyte marker CD8A, or the B-lymphocyte maker CD19. Finally, we found no significant associations between the A(-413)T SNP and HIVE diagnosis, HIV viral loads, or any neuroimmune markers. CONCLUSION:Our data suggest that an individual's HO-1 promoter region (GT)n polymorphism allele repeat length exerts unique modifying risk effects on HIV-induced CNS neuroinflammation and associated neuropathogenesis. Shorter HO-1 (GT)n alleles increase HO-1 promoter activity, which could provide neuroprotection through decreased neuroimmune activation. Therapeutic strategies that induce HO-1 expression could decrease HIV-associated CNS neuroinflammation and decrease the risk for development of HIV neurological disease.

Dataset Information

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

Background

Objective

Methods and results

Conclusion

Publications

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

Similar Datasets

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