title: Endothelial nitric oxide synthase gene variant modulates the relationship between serum cholesterol levels and blood pressure in the general population: new evidence for a direct effect of lipids in arterial blood pressure.
abstract: BACKGROUND
  A causal relationship between plasma cholesterol and blood pressure remains poorly understood. It has been postulated that the decrease in nitric oxide (NO) availability is a potential mechanism by which hypercholesterolemia may stimulate blood pressure elevation. However, evidence supporting the role of the L-arginine-NO pathway on the relationship between hypertension and hypercholesterolemia is still lacking.
  
  
  RESULTS
  We tested for an association of the expressed NO synthase (eNOS) Glu298Asp gene variant and plasma levels of lipids and lipoproteins in the determination of systolic blood pressure levels in a 1577 individuals randomly selected from the general population. Significant interactions could be disclosed either between the Glu298Asp gene variant and total-cholesterol (p = 0.02), log-transformed triglycerides (p = 0.004) or non-HDL-cholesterol (p = 0.003) in the determination of systolic blood pressure. In addition, although the presence of the AspAsp genotype did not significantly increase the risk of hypertension in individuals in the 50% lowest percentile of total-cholesterol, presence of this genotype significantly increased the risk of hypertension in individuals in the 50% highest percentile. Finally, in a multiple logistic regression model adjusting for age, sex, diabetes, ethnicity, smoking status and BMI, the AspAsp genotype significantly increased the risk of hypertension only in individuals with total-cholesterol above 209 mg/dL (p = 0.05, odds ratios (OR) = 2.0).
  
  
  CONCLUSIONS
  Taken together, these results provide evidence supporting the role of the eNOS Glu298Asp gene variant in modulating blood pressure through a relationship with lipid levels.
authors.affiliation: Heart Institute (InCor), São Paulo University Medical School, São Paulo, Brazil.
authors.forename: A C
authors.initials: AC
authors.lastname: Pereira
authors.forename: A C
authors.initials: AC
authors.lastname: Sposito
authors.forename: G F
authors.initials: GF
authors.lastname: Mota
authors.forename: R S
authors.initials: RS
authors.lastname: Cunha
authors.forename: F L
authors.initials: FL
authors.lastname: Herkenhoff
authors.forename: J G
authors.initials: JG
authors.lastname: Mill
authors.forename: J E
authors.initials: JE
authors.lastname: Krieger
mesh_terms: D000328:Adult; D000483:Alleles; D001794:Blood Pressure / Q000502:physiology*; D001938:Brazil / Q000453:epidemiology; D002784:Cholesterol / Q000097:blood*; D003430:Cross-Sectional Studies; D004247:DNA / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000235:genetics / Q000503:physiopathology; D006973:Hypertension / Q000097:blood / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011159:Population Surveillance; D015995:Prevalence; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D004247:DNA; D002784:Cholesterol; D052250:Nitric Oxide Synthase Type III