GT-repeat polymorphism in the heme oxygenase-1 gene promoter and the risk of carotid atherosclerosis related to arsenic exposure
Journal
Journal of Biomedical Science
Journal Volume
17
Journal Issue
1
Pages
70
Date Issued
2010
Author(s)
Wu M.-M.
Chiou H.-Y.
Lee T.-C.
Hsu L.-I.
Wang Y.-H.
Huang W.-L.
Hsieh Y.-C.
Yang T.-Y.
Lee C.-Y.
Yip P.-K.
Wang C.-H.
Hsueh Y.-M.
CHI-LING Chen C.-J.
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 TWN, 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 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. 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. ? 2010 Wu et al; licensee BioMed Central Ltd.
SDGs
Other Subjects
arsenic; heme oxygenase 1; arsenic; heme oxygenase 1; adult; aged; allele; article; cardiovascular risk; carotid atherosclerosis; clinical assessment; cohort analysis; controlled study; disease association; DNA flanking region; Doppler echography; environmental exposure; female; gene; genetic polymorphism; genetic variability; genotype; heterozygote; human; major clinical study; male; priority journal; promoter region; questionnaire; risk factor; Taiwan; carotid artery disease; chemically induced disorder; dinucleotide repeat; echography; gene frequency; genetic polymorphism; genetics; promoter region; risk; statistical model; water pollutant; Arsenic; Carotid Artery Diseases; Dinucleotide Repeats; Gene Frequency; Heme Oxygenase-1; Humans; Logistic Models; Odds Ratio; Polymorphism, Genetic; Promoter Regions, Genetic; Risk Factors; Taiwan; Water Pollutants, Chemical
Type
journal article