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
Journal
Atherosclerosis
Journal Volume
219
Journal Issue
2
Pages
704-708
Date Issued
2011
Author(s)
Wu M.-M.
Chiou H.-Y.
Hsu L.-I.
Lien L.-M.
Wang C.-H.
Hsieh Y.-C.
Wang Y.-H.
Hsueh Y.-M.
Lee T.-C.
Chen C.-J.
Abstract
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= 0.007] 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. ? 2011 Elsevier Ireland Ltd.
SDGs
Other Subjects
arsenic; heme oxygenase 1; triacylglycerol; adult; age distribution; allele; article; body mass; cardiovascular risk; cross-sectional study; diastolic blood pressure; DNA polymorphism; effect size; female; follow up; genetic association; genetic variability; genotype; heterozygote; human; hypertension; longitudinal study; major clinical study; male; mortality; phenotype; priority journal; sex difference; systolic blood pressure; triacylglycerol blood level; Aged; Arsenic; Blood Pressure; Cardiovascular Diseases; China; Cross-Sectional Studies; Environmental Pollutants; Female; Gene Frequency; Gene-Environment Interaction; Genetic Predisposition to Disease; Heme Oxygenase-1; Humans; Hypertension; Linear Models; Logistic Models; Longitudinal Studies; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Phenotype; Polymorphism, Genetic; Promoter Regions, Genetic; Proportional Hazards Models; Repetitive Sequences, Nucleic Acid; Risk Assessment; Risk Factors
Type
journal article