title: GT-repeat polymorphism in the heme oxygenase-1 gene promoter and the risk of carotid atherosclerosis related to arsenic exposure.
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 (< 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.
authors.affiliation: School of Public Health, Taipei Medical University, Taipei, Taiwan. mmwu@tmu.edu.tw
authors.forename: Meei-Maan
authors.initials: MM
authors.lastname: Wu
authors.forename: Hung-Yi
authors.initials: HY
authors.lastname: Chiou
authors.forename: Te-Chang
authors.initials: TC
authors.lastname: Lee
authors.forename: Chi-Ling
authors.initials: CL
authors.lastname: Chen
authors.forename: Ling-I
authors.initials: LI
authors.lastname: Hsu
authors.forename: Yuan-Hung
authors.initials: YH
authors.lastname: Wang
authors.forename: Wen-Ling
authors.initials: WL
authors.lastname: Huang
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Hsieh
authors.forename: Tse-Yen
authors.initials: TY
authors.lastname: Yang
authors.forename: Cheng-Yeh
authors.initials: CY
authors.lastname: Lee
authors.forename: Ping-Keung
authors.initials: PK
authors.lastname: Yip
authors.forename: Chih-Hao
authors.initials: CH
authors.lastname: Wang
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Hsueh
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Chen
mesh_terms: D001151:Arsenic / Q000633:toxicity*; D002340:Carotid Artery Diseases / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000235:genetics*; D018900:Dinucleotide Repeats / Q000235:genetics*; D005787:Gene Frequency; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D013624:Taiwan; D014463:Ultrasonography; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D014874:Water Pollutants, Chemical; D051547:Heme Oxygenase-1; D001151:Arsenic
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