title: Genetic variation in the presynaptic norepinephrine transporter is associated with blood pressure responses to exercise in healthy humans.
abstract: BACKGROUND
  The presynaptic norepinephrine transporter (NET) mediates synaptic clearance and recycling of norepinephrine. NET-deficient transgenic mice have elevated blood pressure (BP), heart rate, and catecholamine concentrations. However, the in-vivo effects of common NET variants on cardiovascular regulation at rest and during exercise are unknown.
  
  
  METHODS
  We studied cardiovascular responses and plasma catecholamine concentrations at rest and during bicycle exercise at increasing workloads (25, 50, and 75 W) in 145 healthy participants. We used multiple linear regressions to analyze the effect of common, purportedly functional polymorphisms in NET (rs2242446 and rs28386840) on cardiovascular measures.
  
  
  RESULTS
  44 and 58.9% of participants carried at least one variant allele for NET T-182C and A-3081T, respectively. Systolic BP during exercise and systolic BP-area under the curve were higher in carriers of variant NET alleles (P=0.003 and 0.009 for T-182C and A-3081T, respectively) and NET haplotype -182C/-3081T compared with -182T/-3081A (all P<0.01). Diastolic BP during exercise was also higher at lower, but not at higher exercise stages in carriers of NET -182C (P<0.01) and -3081T variants (P<0.05). NET genotypes were not associated with catecholamine concentrations or heart rate.
  
  
  CONCLUSIONS
  Common genetic NET variants (-182C and -3081T) are associated with greater BP response to exercise in humans.
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Utkarsh
authors.initials: U
authors.lastname: Kohli
authors.forename: Maureen K
authors.initials: MK
authors.lastname: Hahn
authors.forename: Brett A
authors.initials: BA
authors.lastname: English
authors.forename: Gbenga G
authors.initials: GG
authors.lastname: Sofowora
authors.forename: Mordechai
authors.initials: M
authors.lastname: Muszkat
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.forename: Randy D
authors.initials: RD
authors.lastname: Blakely
authors.forename: C Michael
authors.initials: CM
authors.lastname: Stein
authors.forename: Daniel
authors.initials: D
authors.lastname: Kurnik
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000235:genetics*; D002395:Catecholamines / Q000097:blood; D015331:Cohort Studies; D015444:Exercise / Q000502:physiology*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D002395:Catecholamines; D050484:Norepinephrine Plasma Membrane Transport Proteins; D009638:Norepinephrine