GT-repeat polymorphism in the heme oxygenase-1 gene promoter is associated with cardiovascular mortality risk in an arsenic-exposed population in northeastern Taiwan

Meei Maan Wu, Hung Yi Chiou, Chi Ling Chen, Yuan Hung Wang, Yi Chen Hsieh, Li Ming Lien, Te Chang Lee, Chien Jen Chen

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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.

Original languageEnglish
Pages (from-to)226-233
Number of pages8
JournalToxicology and Applied Pharmacology
Volume248
Issue number3
DOIs
Publication statusPublished - Nov 1 2010

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Keywords

  • Arsenic
  • Cardiovascular mortality
  • Genetic polymorphism
  • Heme oxygenase-1
  • Prospective design

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology
  • Medicine(all)

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