GT-repeat polymorphism in the heme oxygenase-1 gene promoter is associated with cardiovascular mortality risk in an arsenic-exposed population in northeastern Taiwan
Journal
Toxicology and Applied Pharmacology
Journal Volume
248
Journal Issue
3
Pages
226-233
Date Issued
2010
Author(s)
Abstract
Inorganic arsenic has been associated with increased risk of atherosclerotic vascular disease and mortality in humans. A functional GT-repeat polymorphism in the heme oxygenase-1 (HO-1) gene promoter is inversely correlated with the development of coronary artery disease and restenosis after clinical angioplasty. The relationship of HO-1 genotype with arsenic-associated cardiovascular disease has not been studied. In this study, we evaluated the relationship between the HO-1 GT-repeat polymorphism and cardiovascular mortality in an arsenic-exposed population. A total of 504 study participants were followed up for a median of 10.7 years for occurrence of cardiovascular deaths (coronary heart disease, cerebrovascular disease, and peripheral arterial disease). Cardiovascular risk factors and DNA samples for determination of HO-1 GT repeats were obtained at recruitment. GT repeats variants were grouped into the S (< 27 repeats) or L allele (? 27 repeats). Relative mortality risk was estimated using Cox regression analysis, adjusted for competing risk of cancer and other causes. For the L/L, L/S, and S/S genotype groups, the crude mortalities for cardiovascular disease were 8.42, 3.10, and 2.85 cases/1000 person-years, respectively. After adjusting for conventional cardiovascular risk factors and competing risk of cancer and other causes, carriers with class S allele (L/S or S/S genotypes) had a significantly reduced risk of cardiovascular mortality compared to non-carriers (L/L genotype) [OR, 0.38; 95% CI, 0.16-0.90]. In contrast, no significant association was observed between HO-1 genotype and cancer mortality or mortality from other causes. Shorter (GT)n repeats in the HO-1 gene promoter may confer protective effects against cardiovascular mortality related to arsenic exposure. ? 2010 Elsevier Inc.
Subjects
Arsenic; Cardiovascular mortality; Genetic polymorphism; Heme oxygenase-1; Prospective design
SDGs
Other Subjects
arsenic; heme oxygenase 1; arsenic; heme oxygenase 1; adult; artery disease; article; cancer risk; cardiovascular risk; cerebrovascular disease; controlled study; DNA structure; female; follow up; genetic association; genetic polymorphism; genotype; heterozygote; human; ischemic heart disease; major clinical study; male; mortality; population genetics; population research; promoter region; proportional hazards model; prospective study; Taiwan; tandem repeat; aged; Cardiovascular Diseases; cohort analysis; comparative study; dinucleotide repeat; drug effects; environmental exposure; epidemiology; genetics; middle aged; mortality; randomized controlled trial; risk factor; Aged; Arsenic; Cardiovascular Diseases; Cohort Studies; Dinucleotide Repeats; Environmental Exposure; Female; Heme Oxygenase-1; Humans; Male; Middle Aged; Polymorphism, Genetic; Promoter Regions, Genetic; Risk Factors; Taiwan; Aged; Arsenic; Cardiovascular Diseases; Cohort Studies; Dinucleotide Repeats; Environmental Exposure; Female; Heme Oxygenase-1; Humans; Male; Middle Aged; Polymorphism, Genetic; Promoter Regions, Genetic; Risk Factors; Taiwan
Type
journal article