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

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

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.

Original languageEnglish
Article number70
JournalJournal of Biomedical Science
Volume17
Issue number1
DOIs
Publication statusPublished - 2010

Fingerprint

Heme Oxygenase-1
Carotid Artery Diseases
Arsenic
Polymorphism
Genes
Alleles
Atherosclerosis
Association reactions
Oxidative stress
5' Flanking Region
Groundwater
Genetic Polymorphisms
Angioplasty
Carotid Arteries
Regression analysis
Drinking Water
Logistics
Coronary Artery Disease
Oxidative Stress
Logistic Models

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Cell Biology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism
  • Pharmacology (medical)

Cite this

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.

In: Journal of Biomedical Science, Vol. 17, No. 1, 70, 2010.

Research output: Contribution to journalArticle

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. / GT-repeat polymorphism in the heme oxygenase-1 gene promoter and the risk of carotid atherosclerosis related to arsenic exposure. In: Journal of Biomedical Science. 2010 ; Vol. 17, No. 1.
@article{f6d8d42101b448bab398f3153928f270,
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 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.",
author = "Wu, {Meei Maan} and Chiou, {Hung Yi} and Lee, {Te Chang} and Chen, {Chi Ling} and Hsu, {Ling I.} and Wang, {Yuan Hung} and Huang, {Wen Ling} and Hsieh, {Yi Chen} and Yang, {Tse Yen} and Lee, {Cheng Yeh} and Yip, {Ping Keung} and Wang, {Chih Hao} and Hsueh, {Yu Mei} and Chen, {Chien Jen}",
year = "2010",
doi = "10.1186/1423-0127-17-70",
language = "English",
volume = "17",
journal = "Journal of Biomedical Science",
issn = "1021-7770",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - GT-repeat polymorphism in the heme oxygenase-1 gene promoter and the risk of carotid atherosclerosis related to arsenic exposure

AU - Wu, Meei Maan

AU - Chiou, Hung Yi

AU - Lee, Te Chang

AU - Chen, Chi Ling

AU - Hsu, Ling I.

AU - Wang, Yuan Hung

AU - Huang, Wen Ling

AU - Hsieh, Yi Chen

AU - Yang, Tse Yen

AU - Lee, Cheng Yeh

AU - Yip, Ping Keung

AU - Wang, Chih Hao

AU - Hsueh, Yu Mei

AU - Chen, Chien Jen

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77955951478&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955951478&partnerID=8YFLogxK

U2 - 10.1186/1423-0127-17-70

DO - 10.1186/1423-0127-17-70

M3 - Article

C2 - 20796278

AN - SCOPUS:77955951478

VL - 17

JO - Journal of Biomedical Science

JF - Journal of Biomedical Science

SN - 1021-7770

IS - 1

M1 - 70

ER -