title: Catecholamine pathway gene variation is associated with norepinephrine and epinephrine concentrations at rest and after exercise.
abstract: OBJECTIVE
  To examine the hypothesis that genetic variation in enzymes and transporters associated with synthesis, storage, release, and metabolism of catecholamines contributes to the interindividual variability in plasma catecholamine concentrations at rest and after exercise.
  
  
  METHODS
  We measured plasma norepinephrine (NE) and epinephrine concentrations at rest and after a standardized exercise protocol in 165 healthy individuals (60% White, 40% African-American) and examined 29 functional or common variants in 14 genes involved in synthesis, transport, or metabolism of catecholamines. We examined the relationship between genotypes and NE concentrations at rest and the increase after exercise (ΔNE) by multiple linear regression with adjustment for covariates [age, race, sex, BMI, fitness, and resting NE (for ΔNE)]. As a secondary outcome, we carried out similar analyses for epinephrine concentrations.
  
  
  RESULTS
  There was large interindividual variability in resting NE (mean, 204±102 pg/ml; range, 39-616 pg/ml) and ΔNE (mean, 256±206 pg/ml; range, -97 to 953 pg/ml). Resting NE was significantly associated with variants of four genes: CYB561 (P<0.001), VMAT2 (P=0.016), CHGA (P=0.039), and PNMT (P=0.038). ΔNE after exercise was associated with three variants of PNMT (P=0.041) and COMT (P=0.033 and 0.035), and resting and exercise epinephrine concentrations were associated with two variants each.
  
  
  CONCLUSIONS
  The findings of this exploratory study suggest that variation in catecholamine pathway genes contributes to the interindividual variability in plasma NE and epinephrine concentrations at rest and after exercise.
authors.affiliation: Department of Medicine, Division of Clinical, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Laxmi V
authors.initials: LV
authors.lastname: Ghimire
authors.forename: Utkarsh
authors.initials: U
authors.lastname: Kohli
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.forename: Gbenga G
authors.initials: GG
authors.lastname: Sofowora
authors.forename: Mordechai
authors.initials: M
authors.lastname: Muszkat
authors.forename: Eitan A
authors.initials: EA
authors.lastname: Friedman
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Solus
authors.forename: Alastair J J
authors.initials: AJ
authors.lastname: Wood
authors.forename: C Michael
authors.initials: CM
authors.lastname: Stein
authors.forename: Daniel
authors.initials: D
authors.lastname: Kurnik
mesh_terms: D000328:Adult; D044383:Black People / Q000235:genetics; D002395:Catecholamines / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D053379:Chromogranin A / Q000235:genetics; D002986:Clinical Trials as Topic; D003573:Cytochrome b Group / Q000235:genetics; D004837:Epinephrine / Q000097:blood*; D015444:Exercise / Q000502:physiology; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways; D009638:Norepinephrine / Q000097:blood*; D012146:Rest / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000235:genetics; D050493:Vesicular Monoamine Transport Proteins / Q000235:genetics; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: C506150:CHGA protein, human; C521362:CYB561D2 protein, human; D002395:Catecholamines; D053379:Chromogranin A; D003573:Cytochrome b Group; C493452:SLC18A2 protein, human; D025521:Tumor Suppressor Proteins; D050493:Vesicular Monoamine Transport Proteins; D009638:Norepinephrine; D004837:Epinephrine