title: Relationship between the platelet activating factor acetylhydrolase gene and intractability of ulcerative colitis.
abstract: OBJECTIVE
  Platelet activating factor, which is a potent mediator of inflammatory injury in ulcerative colitis, is inactivated by platelet activating factor acetylhydrolase. Recently, a point mutation (G994 to T transversion) was observed in exon 9 of the platelet activating factor acetylhydrolase gene, and this mutation was found to be associated with a decrease in platelet activating factor acetylhydrolase activity in plasma. The aim of this study was to determine whether the gene mutation was associated with the severity of ulcerative colitis.
  
  
  METHODS
  We studied 53 patients with ulcerative colitis and 108 control subjects. The plasma platelet activating factor acetylhydrolase genotype was determined as representative cases with three different genotypes (GG, GT, and TT) by an allele-specific polymerase chain reaction.
  
  
  RESULTS
  There was no significant difference in genotypic frequency (GG, GT, and TT genotype frequencies were 68, 30, and 2 percent in controls and 55, 45, and 0 percent in ulcerative colitis patients). Platelet activating factor acetylhydrolase activity in plasma was also measured and did not differ significantly between ulcerative colitis patients and controls (1.50+/-0.12 vs. 1.81+/-0.34 nmol/min/50 microl, P = 0.60). However, according to the relationship between the platelet activating factor acetylhydrolase gene mutation and clinical characteristics of ulcerative colitis patients, the operative ratio cause of unresponsiveness to steroid therapy was significantly higher in patients with the GT genotype than in those with the GG genotype (66.7 vs. 27.6 percent, P = 0.019).
  
  
  CONCLUSIONS
  We conclude that steroid-nonresponsive ulcerative colitis patients have a high frequency of the platelet activating factor acetylhydrolase gene mutation. Therefore, genotyping of this gene may be a useful marker to predict responsiveness to steroid therapy.
authors.affiliation: Department of Surgery II, Hamamatsu University School of Medicine, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Nakamura
authors.forename: Takanori
authors.initials: T
authors.lastname: Sakaguchi
authors.forename: Naoki
authors.initials: N
authors.lastname: Unno
authors.forename: Junko
authors.initials: J
authors.lastname: Sugatani
authors.forename: Masao
authors.initials: M
authors.lastname: Miwa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nakamura
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D006867:Hydrolases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010972:Platelet Activating Factor / Q000031:analogs & derivatives* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012720:Severity of Illness Index; D013256:Steroids
chemical_list: D000893:Anti-Inflammatory Agents; D010972:Platelet Activating Factor; D013256:Steroids; D006867:Hydrolases