title: Pathophysiological analysis of primary biliary cirrhosis focusing on choline/phospholipid metabolism.
abstract: OBJECTIVE
  Injury to biliary epithelial cells caused by disorders in bile composition may be the initial step in the pathogenesis of primary biliary cirrhosis (PBC). We therefore examined choline/phospholipid metabolism in livers of patients with PBC.
  
  
  METHODS
  Hepatic levels of mRNA encoded by choline metabolism-related genes in early stage PBC patients were quantified by real-time RT-PCR. Serum cholesterol and triglyceride concentrations in each lipoprotein compartment and serum/tissue choline levels were also measured. OCT1 expression was quantified by genotype (rs683369 and rs622342).
  
  
  RESULTS
  Serum choline concentrations were significantly higher in PBC patients than in normal individuals, with the concentrations in the former lowered by treatment with fibrates. Hepatic choline levels were markedly lower in PBC patients than in controls. The levels of expression of genes associated with choline uptake (OCT1 and CTL1), phosphatidylcholine synthesis (PEMT and BHMT), and phosphatidylcholine transport (MDR3) were significantly upregulated in PBC compared with control livers. Serum cholesterol concentrations and the cholesterol/triglyceride ratio in serum very low density lipoprotein were markedly higher in PBC patients than in controls. In PBC liver, OCT1 protein levels were lower in patients with minor (CG/GG at rs683369 and/or CC at rs622342) than major (CC at rs683369 and AA at rs622342) genotypes of the OCT1 gene.
  
  
  CONCLUSIONS
  During early stage PBC, hepatocellular choline uptake and PC synthesis become dysregulated. OCT1 genotypes may influence the pathogenesis of PBC.
authors.affiliation: Department of Gastroenterology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Kohjima
authors.forename: Munechika
authors.initials: M
authors.lastname: Enjoji
authors.forename: Ryoko
authors.initials: R
authors.lastname: Yada
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yoshimoto
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Nakamura
authors.forename: Kunitaka
authors.initials: K
authors.lastname: Fukuizumi
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Fukushima
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Murata
authors.forename: Manabu
authors.initials: M
authors.lastname: Nakashima
authors.forename: Masaki
authors.initials: M
authors.lastname: Kato
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kotoh
authors.forename: Ken
authors.initials: K
authors.lastname: Shirabe
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakajima
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Nozaki
authors.forename: Akira
authors.initials: A
authors.lastname: Honda
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Matsuzaki
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakamuta
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002794:Choline / Q000378:metabolism*; D005260:Female; D022781:Hepatocytes / Q000201:enzymology*; D006801:Humans; D050356:Lipid Metabolism; D008105:Liver Cirrhosis, Biliary / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D027702:Organic Cation Transporter 1 / Q000235:genetics / Q000378:metabolism; D010713:Phosphatidylcholines / Q000096:biosynthesis* / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide
chemical_list: D027702:Organic Cation Transporter 1; D010713:Phosphatidylcholines; D010743:Phospholipids; D002794:Choline
keywords: MDR3; OCT1; cholesterol; choline; phospholipids; primary biliary cirrhosis