title: Plasma choline depletion is associated with decreased peripheral blood leukocyte acetylcholine in children with cystic fibrosis.
abstract: BACKGROUND
  Choline is an important constituent of acetylcholine. Choline is needed for acetylcholine in the nonneuronal acetylcholine system that includes epithelial cells of the lung and intestine, endothelial cells, and immune cells. Plasma free choline concentrations are low in children with cystic fibrosis (CF), but the implications for acetylcholine are unknown.
  
  
  OBJECTIVE
  We determined the relation between plasma free choline and related metabolites and leukocyte acetylcholine in children with CF and in a control group of healthy children without CF.
  
  
  METHODS
  This was a cross-sectional study in 34 children with CF who were pancreatic insufficient and taking pancreatic enzyme-replacement therapy and in 16 healthy children. Plasma free choline, betaine, dimethylglycine, methionine, homocysteine, and leukocyte acetylcholine concentrations were quantified by using isotope-dilution HPLC-tandem mass spectrometry.
  
  
  RESULTS
  Mean (±SE) plasma free choline was 9.30 ± 0.37 and 6.54 ± 0.38 μmol/L (P < 0.05) and leukocyte acetylcholine was 1.21 ± 0.016 and 0.077 ± 0.011 pmol leukocyte acetylcholine/10(6) cells (P < 0.05) in control children and children with CF, respectively. Leukocyte acetylcholine was positively correlated with plasma free choline concentration in children with CF (r = 0.412, P < 0.05) but not in control children. Plasma betaine, dimethylglycine, and methionine concentrations were also lower in children with CF than in control children (P < 0.05).
  
  
  CONCLUSIONS
  A low free choline and methyl status in children with CF is associated with reduced acetylcholine in leukocytes. Whether these changes are explained by a mutation in the CF transmembrane conductance regulator or disturbances in choline metabolism and the implications for immune cell dysfunction in CF are unknown. This trial was registered at clinicaltrials.gov as NCT01150136.
authors.affiliation: Nutrition and Metabolism Research Program, Child and Family Research Institute, Department of Paediatrics, University of British Columbia, Vancouver, Canada. sinnis@interchange.ubc.ca
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Innis
authors.forename: A George F
authors.initials: AG
authors.lastname: Davidson
authors.forename: Benjamin N
authors.initials: BN
authors.lastname: Bay
authors.forename: Penelope J
authors.initials: PJ
authors.lastname: Slack
authors.forename: David
authors.initials: D
authors.lastname: Hasman
mesh_terms: D000109:Acetylcholine / Q000097:blood*; D000293:Adolescent; D001622:Betaine / Q000097:blood; D002648:Child; D002675:Child, Preschool; D002794:Choline / Q000097:blood*; D003430:Cross-Sectional Studies; D003550:Cystic Fibrosis / Q000097:blood* / Q000628:therapy; D056947:Enzyme Replacement Therapy; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008715:Methionine / Q000097:blood; D010194:Pancreatin / Q000627:therapeutic use; D012521:Sarcosine / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D001622:Betaine; C025138:dimethylglycine; D010194:Pancreatin; D008715:Methionine; D002794:Choline; D000109:Acetylcholine; D012521:Sarcosine