title: Polymorphisms of endothelial nitric oxide synthase gene in systolic heart failure: an haplotype analysis.
abstract: BACKGROUND
  Endothelial nitric oxide synthase (eNOS) gene polymorphisms have been associated with the pathogenesis of cardiovascular diseases, but few studies have evaluated the role of eNOS haplotypes on the risk and prognosis of heart failure (HF). This prospective study was designed to analyze the impact of three eNOS polymorphisms (T-786C, VNTR4a/b and Glu298Asp) and their haplotypes on the susceptibility and clinical outcomes in HF outpatients with systolic dysfunction.
  
  
  RESULTS
  We conducted a case-control and a cohort study in which 316 HF patients and 360 healthy controls were recruited from a tertiary care university hospital. DNA was extracted from peripheral blood and eNOS polymorphisms were detected by PCR or PCR-RFLP. Patients were predominantly men, had a mean left ventricular ejection fraction of 31% and were followed-up for a median of 41months; there were 96 deaths, including 58 HF-related deaths. Genotype distribution of the eNOS T-786C, VNTR 4a/b and Glu298Asp was similar between HF patients and controls. Haplotype frequencies differed between HF patients and controls only in African-Brazilians (p=0.043). African-Brazilian patients that carried the haplotype -786C/4b/Asp298 had a better prognosis than patients that carried other haplotypes (log rank p value=0.016 for all-cause mortality). In a Cox proportional hazard model adjusted for clinical variables of risk, the -786C/4b/Asp298 haplotype remained as an independent genetic predictor of survival (adjusted HR=0.11; 95% CI=0.01-0.83; p=0.03).
  
  
  CONCLUSIONS
  The -786C/4b/Asp298 eNOS haplotype had a significant impact on HF susceptibility and prognosis, particularly in African-Brazilian patients.
authors.affiliation: Cardiovascular Experimental and Molecular Laboratory, The Heart Failure and Cardiac Transplant Unit, Cardiology Division at Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Nidiane C
authors.initials: NC
authors.lastname: Martinelli
authors.forename: Kátia G
authors.initials: KG
authors.lastname: Santos
authors.forename: Andréia
authors.initials: A
authors.lastname: Biolo
authors.forename: Vanessa L
authors.initials: VL
authors.lastname: La Porta
authors.forename: Carolina R
authors.initials: CR
authors.lastname: Cohen
authors.forename: Daiane
authors.initials: D
authors.lastname: Silvello
authors.forename: Michael E
authors.initials: ME
authors.lastname: Andrades
authors.forename: Nadine
authors.initials: N
authors.lastname: Clausell
authors.forename: Luis E
authors.initials: LE
authors.lastname: Rohde
mesh_terms: D000368:Aged; D044383:Black People / Q000706:statistics & numerical data; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006333:Heart Failure / Q000201:enzymology* / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D011446:Prospective Studies; D044465:White People / Q000706:statistics & numerical data
chemical_list: D052250:Nitric Oxide Synthase Type III