- 作者: Meei-Maan Wu; Hung-Yi Chiou; Te-Chang Lee; Chi-Ling Chen; Ling-I Hsu; Yuan-Hung Wang; Wen-Ling Huang; Yi-Chen Hsieh; Tse-Yen Yang; Cheng-Yeh Lee; Ping-Keung Yip; Chih-Hao Wang; Yu-Mei Hsueh; Chien-Jen Chen
- 作者服務機構: School of Public Health, Taipei Medical University, Taipei, Taiwan, R.O.C.
- 中文摘要: --
- 英文摘要:
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. - 中文關鍵字: --
- 英文關鍵字: --