title: Polymorphisms of microsomal triglyceride transfer protein gene and manganese superoxide dismutase gene in non-alcoholic steatohepatitis.
abstract: OBJECTIVE
  The pathogenesis of non-alcoholic steatohepatitis (NASH) is poorly understood. The aim of this study was to examine genetic influences on NASH pathogenesis.
  
  
  METHODS
  Blood samples from 63 patients with biopsy-proven NASH and 150 healthy controls were analyzed by the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Two functional polymorphisms were studied: the -493 G/T polymorphism in the promoter of microsomal triglyceride transfer protein (MTP) and the 1183 T/C polymorphism in the mitochondrial targeting sequence of manganese superoxide dismutase (MnSOD).
  
  
  RESULTS
  NASH patients had a much higher incidence of the MTP gene G allele (P=0.001) and of the G/G genotype (P=0.002) compared to the controls. Fat occupied more area in liver lobules and the stage of NASH was advanced in patients with the G/G-genotype than in patients with G/T-genotype (P=0.04). NASH patients also had a higher incidence of the MnSOD T/T genotype (P=0.016).
  
  
  CONCLUSIONS
  The G allele in the MTP promoter leads to decreased MTP transcription, less export of triglyceride from hepatocytes, and greater intracellular triglyceride accumulation. The T allele in MnSOD mitochondrial targeting sequence leads to less transport of MnSOD to the mitochondria. Therefore, functional polymorphisms in MTP and MnSOD may be involved in determining susceptibility of NASH.
authors.affiliation: Department of Gastroenterology and Hepatology, Kochi Medical School, Nankoku 783-8505 Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Namikawa
authors.forename: Zhang
authors.initials: Z
authors.lastname: Shu-Ping
authors.forename: John Raynor
authors.initials: JR
authors.lastname: Vyselaar
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Nozaki
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nemoto
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ono
authors.forename: Naoaki
authors.initials: N
authors.lastname: Akisawa
authors.forename: Toshiji
authors.initials: T
authors.lastname: Saibara
authors.forename: Makoto
authors.initials: M
authors.lastname: Hiroi
authors.forename: Hideaki
authors.initials: H
authors.lastname: Enzan
authors.forename: Saburo
authors.initials: S
authors.lastname: Onishi
mesh_terms: D000328:Adult; D000447:Aldehydes / Q000378:metabolism; D000483:Alleles; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics; D005234:Fatty Liver / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D006521:Hepatitis, Chronic / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D013482:Superoxide Dismutase / Q000235:genetics*; D013577:Syndrome
chemical_list: D000447:Aldehydes; D002352:Carrier Proteins; C106092:microsomal triglyceride transfer protein; D004247:DNA; D013482:Superoxide Dismutase; C027576:4-hydroxy-2-nonenal