GT-repeat polymorphism in the heme oxygenase-1 gene promoter is associated with cardiovascular mortality risk in an arsenic-exposed population in northeastern Taiwan.
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.
Wu
Meei-Maan
MM
School of Public Health, Taipei Medical University, Taipei, Taiwan. mmwu@tmu.edu.tw
Chiou
Hung-Yi
HY
Chen
Chi-Ling
CL
Wang
Yuan-Hung
YH
Hsieh
Yi-Chen
YC
Lien
Li-Ming
LM
Lee
Te-Chang
TC
Chen
Chien-Jen
CJ
D000368:Aged; D001151:Arsenic / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000235:genetics* / Q000401:mortality*; D015331:Cohort Studies; D018900:Dinucleotide Repeats / Q000187:drug effects / Q000235:genetics*; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000187:drug effects / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics*; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology
D051547:Heme Oxygenase-1; D001151:Arsenic