title: Abnormally low serum acylcarnitine levels in narcolepsy patients.
abstract: BACKGROUND
  Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness, cataplexy, and REM sleep abnormalities. A genome-wide association study identified a novel narcolepsy-related single nucleotide polymorphism (SNP), rs5770917, which is located adjacent to CPT1B (carnitine palmitoyltransferase 1B). In this study, we analyzed the CPT1B expression level and measured the carnitine fractions in blood samples obtained from narcolepsy patients and control subjects to test the hypothesis that fatty acid β-oxidation is altered in narcolepsy.
  
  
  RESULTS
  We measured CPT1B mRNA expression in white blood cells of 38 narcolepsy patients and 56 healthy control subjects. The serum carnitine fractions (total carnitine, free carnitine, and acylcarnitine) were measured in the 38 narcolepsy patients and in 30 of 56 control subjects. Stepwise multiple regression analysis revealed that the risk allele (C) for SNP rs5770917 was significantly associated with decreased CPT1B mRNA expression (P = 1.0 × 10(-9)), and the CPT1B expression was higher in the narcolepsy patients than in the controls (P = 0.005). The acylcarnitine levels were abnormally low in 21% of the narcolepsy patients while those of all the controls were within the normal range. Stepwise multiple regression analysis using the dichotomous variable for acylcarnitine (normal or abnormal) as an objective variable revealed that the diagnosis of narcolepsy but not CPT1B expression level and BMI was associated with abnormally low acylcarnitine levels (P = 0.006).
  
  
  CONCLUSIONS
  Our results indicate that multiple factors are involved in the regulation of serum acylcarnitine levels. Abnormally low levels of acylcarnitine observed in narcolepsy suggest dysfunctional fatty acid β-oxidation pathway.
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan. miyagawa-taku@umin.ac.jp
authors.forename: Taku
authors.initials: T
authors.lastname: Miyagawa
authors.forename: Hiroko
authors.initials: H
authors.lastname: Miyadera
authors.forename: Susumu
authors.initials: S
authors.lastname: Tanaka
authors.forename: Minae
authors.initials: M
authors.lastname: Kawashima
authors.forename: Mihoko
authors.initials: M
authors.lastname: Shimada
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Honda
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.forename: Makoto
authors.initials: M
authors.lastname: Honda
mesh_terms: D000328:Adult; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009290:Narcolepsy / Q000097:blood* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C116917:acylcarnitine; C542591:CPT1B protein, human; D002334:Carnitine O-Palmitoyltransferase; D002331:Carnitine