Journal of Biomedical Science (Aug 2010)

GT-repeat polymorphism in the heme oxygenase-1 gene promoter and the risk of carotid atherosclerosis related to arsenic exposure

  • Wu Meei-Maan,
  • Chiou Hung-Yi,
  • Lee Te-Chang,
  • Chen Chi-Ling,
  • Hsu Ling-I,
  • Wang Yuan-Hung,
  • Huang Wen-Ling,
  • Hsieh Yi-Chen,
  • Yang Tse-Yen,
  • Lee Cheng-Yeh,
  • Yip Ping-Keung,
  • Wang Chih-Hao,
  • Hsueh Yu-Mei,
  • Chen Chien-Jen

DOI
https://doi.org/10.1186/1423-0127-17-70
Journal volume & issue
Vol. 17, no. 1
p. 70

Abstract

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Abstract 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 ( 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 (