title: Habitual energy expenditure modifies the association between NOS3 gene polymorphisms and blood pressure.
abstract: BACKGROUND
  The endothelial nitric-oxide synthase (NOS3) gene encodes the enzyme (eNOS) that synthesizes the molecule nitric oxide, which facilitates endothelium-dependent vasodilation in response to physical activity. Thus, energy expenditure may modify the association between the genetic variation at NOS3 and blood pressure.
  
  
  METHODS
  To test this hypothesis, we genotyped 11 NOS3 polymorphisms, capturing all common variations, in 726 men and women from the Medical Research Council (MRC) Ely Study (age (mean +/- s.d.): 55 +/- 10 years, body mass index: 26.4 +/- 4.1 kg/m(2)). Habitual/non-resting energy expenditure (NREE) was assessed via individually calibrated heart rate monitoring over 4 days.
  
  
  RESULTS
  The intronic variant, IVS25+15 [G-->A], was significantly associated with blood pressure; GG homozygotes had significantly lower levels of diastolic blood pressure (DBP) (-2.8 mm Hg; P = 0.016) and systolic blood pressure (SBP) (-1.9 mm Hg; P = 0.018) than A-allele carriers. The interaction between NREE and IVS25+15 was also significant for both DBP (P = 0.006) and SBP (P = 0.026), in such a way that the effect of the GG-genotype on blood pressure was stronger in individuals with higher NREE (DBP: -4.9 mm Hg, P = 0.02. SBP: -3.8 mm Hg, P= 0.03 for the third tertile). Similar results were observed when the outcome was dichotomously defined as hypertension.
  
  
  CONCLUSIONS
  In summary, the NOS3 IVS25+15 is directly associated with blood pressure and hypertension in white Europeans. However, the associations are most evident in the individuals with the highest NREE. These results need further replication and have to be ideally tested in a trial before being informative for targeted disease prevention. Eventually, the selection of individuals for lifestyle intervention programs could be guided by knowledge of genotype.
authors.affiliation: Medical Research Council Epidemiology Unit, Institute of Metabolic Science, Cambridge, UK. vks22@medschl.cam.ac.uk
authors.forename: Karani S
authors.initials: KS
authors.lastname: Vimaleswaran
authors.forename: Paul W
authors.initials: PW
authors.lastname: Franks
authors.forename: Inês
authors.initials: I
authors.lastname: Barroso
authors.forename: Soren
authors.initials: S
authors.lastname: Brage
authors.forename: Ulf
authors.initials: U
authors.lastname: Ekelund
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wareham
authors.forename: Ruth J F
authors.initials: RJ
authors.lastname: Loos
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001794:Blood Pressure / Q000235:genetics* / Q000502:physiology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004734:Energy Metabolism / Q000235:genetics* / Q000502:physiology; D005260:Female; D005838:Genotype; D006339:Heart Rate / Q000502:physiology; D006720:Homozygote; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology; D008019:Life Style; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D044465:White People / Q000235:genetics
chemical_list: C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III