title: 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.
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.
authors.affiliation: School of Public Health, Taipei Medical University, 250 Wu-Hsing Street, Taipei 11031, Taiwan. mmwu@tmu.edu.tw
authors.forename: Meei-Maan
authors.initials: MM
authors.lastname: Wu
authors.forename: Hung-Yi
authors.initials: HY
authors.lastname: Chiou
authors.forename: Chi-Ling
authors.initials: CL
authors.lastname: Chen
authors.forename: Ling-I
authors.initials: LI
authors.lastname: Hsu
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Lien
authors.forename: Chih-Hao
authors.initials: CH
authors.lastname: Wang
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Hsieh
authors.forename: Yuan-Hung
authors.initials: YH
authors.lastname: Wang
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Hsueh
authors.forename: Te-Chang
authors.initials: TC
authors.lastname: Lee
authors.forename: Wen-Fang
authors.initials: WF
authors.lastname: Cheng
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Chen
mesh_terms: D000368:Aged; D001151:Arsenic / Q000009:adverse effects*; D001794:Blood Pressure / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology; D002681:China / Q000453:epidemiology; D003430:Cross-Sectional Studies; D004785:Environmental Pollutants / Q000009:adverse effects*; D005260:Female; D005787:Gene Frequency; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology; D016014:Linear Models; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D012091:Repetitive Sequences, Nucleic Acid; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D004785:Environmental Pollutants; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D001151:Arsenic