Association of heme oxygenase-1 GT-repeat polymorphism with blood pressure phenotypes and its relevance to future cardiovascular mortality risk: An observation based on arsenic-exposed individuals

Objective: Heme oxygenase (HO)-1 is up-regulated as a cellular defense responding to stressful stimuli in experimental studies. A GT-repeat length polymorphism in the HO-1 gene promoter was inversely correlated to HO-1 induction. Here, we reported the association of GT-repeat polymorphism with blood pressure (BP) phenotypes, and their interaction on cardiovascular (CV) mortality risk in arsenic-exposed cohorts. Methods: Associations of GT-repeat polymorphism with BP phenotypes were investigated at baseline in a cross-sectional design. Effect of GT-repeat polymorphism on CV mortality was investigated in a longitudinal design stratified by hypertension. GT-repeat variants were grouped by S (<27 repeats) or L (>= 27 repeats) alleles. Multivariate analyses were used to estimate the effect size after accounting for CV covariates. Results: Totally, 894 participants were recruited and analyzed. At baseline, carriers with HO-1 S alleles had lower diastolic BP (L/S genotypes, P=0.014) and a lower possibility of being hypertensive (L/S genotypes, P=0.048). After follow-up, HO-1 S allele was significantly associated with a reduced CV risk in hypertensive participants [relative mortality ratio (RMR) 0.27 (CI 0.11, 0.69), P=0.00] but not in normotensive. Hypertensive participants without carrying the S allele had a 5.23-fold increased risk [RMR 5.23 (CI 1.99, 13.69), P=0.0008] of CV mortality compared with normotensive carrying the S alleles. Conclusions: HO-1 short GT-repeat polymorphism may play a protective role in BP regulation and CV mortality risk in hypertensive individuals against environmental stressors. (C) 2011 Elsevier Ireland Ltd. All rights reserved.