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Research
GT-repeat polymorphism in the heme oxygenase-1 gene promoter and the risk of carotid atherosclerosis related to arsenic exposure
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* Corresponding authors: Meei-Maan Wu mmwu@tmu.edu.tw - Hung-Yi Chiou hychiou@tmu.edu.tw
1 School of Public Health, Taipei Medical University, Taipei, Taiwan
2 Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan
3 Graduate Institute of Basic Medicine, College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan
4 Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
5 Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
6 Genomics Research Center, Academia Sinica, Taipei, Taiwan
7 Center of Excellence for Cancer Research, Taipei Medical University, Taipei, Taiwan
8 School of Medicine, College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan
9 Department of Cardiology, Cardinal Tien Hospital, College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan
Journal of Biomedical Science 2010, 17:70 doi:10.1186/1423-0127-17-70
Published: 26 August 2010Abstract
Background
Arsenic 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.
Methods
Three-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.
Results
Analysis 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 μg/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.
Conclusions
This 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.