title: Association analyses of genetic polymorphisms of GSTM1, GSTT1, NQO1, NAT2, LPL, PRSS1, PSTI, and CFTR with chronic alcoholic pancreatitis in Japan.
abstract: BACKGROUND
  Excessive consumption of alcohol is involved in the onset of pancreatitis. However, most of heavy drinkers do not always develop chronic pancreatitis. Various genetic factors appear to be involved in these individual differences in onset of chronic alcoholic pancreatitis. Here we investigated a possible association of alcoholic pancreatitis with polymorphisms of the various genes belong to the phase II detoxification enzymes responsible for metabolism of the oxidative compounds, and the several genes that have relevance to inherited pancreatitis.
  
  
  METHODS
  The subjects consisted of 53 patients with chronic alcoholic pancreatitis, 54 alcoholic patients without pancreatic dysfunction, and 42 healthy individuals. DNA was extracted from the peripheral nucleated blood cells of all subjects and genetic mutations and subtypes were analyzed by the PCR and RFLP methods. We examined the correlation between chronic alcoholic pancreatitis and variants of the phase II detoxification enzymes such as Glutathione S-transferase M1 (GSTM1), glutathione S-transferase theta 1 (GSTT1), NADPH-quinone oxidoreductase 1 (NQO1), and N-acetyl transferase (NAT2). In addition, genes of lipoprotein lipase (LPL), cationic trypsinogen (PRSS1), pancreatic secretory trypsin inhibitor (PSTI), and cystic fibrosis transmembrane conductance regulator (CFTR) were also analyzed.
  
  
  RESULTS
  Frequencies of the gene deletion of GSTM1 and GSTT1 in addition to the C-allele frequency of NQO1 tended to be higher in the alcoholic patients with (AlCP) or without pancreatic dysfunction (Alc) than in the healthy controls although the difference was not significant. The NAT2 gene showed no relation with Alc and AlCP patients. PSTI, LPL, PRSS1, and CFTR genes presented no association with chronic alcoholic pancreatitis.
  
  
  CONCLUSIONS
  All genes analyzed in the present study lacked association with chronic alcoholic pancreatitis. However, the gene deletion of GSTM1 and GSTT1, and the C-allele of NQO1 cannot be ruled out for association with alcoholism.
authors.affiliation: Department of Internal Medicine, National Hospital Organization Kurihama Alcoholism Center, 5-3-1 Nobi, Yokosuka-shi, Kanagawa 239-0841, Japan. maruyaka@kurihama.hosp.go.jp
authors.forename: Katsuya
authors.initials: K
authors.lastname: Maruyama
authors.forename: Shoji
authors.initials: S
authors.lastname: Harada
authors.forename: Akira
authors.initials: A
authors.lastname: Yokoyama
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mizukami
authors.forename: Satoru
authors.initials: S
authors.lastname: Naruse
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hirota
authors.forename: Isao
authors.initials: I
authors.lastname: Nishimori
authors.forename: Makoto
authors.initials: M
authors.lastname: Otsuki
mesh_terms: D000328:Adult; D000368:Aged; D001191:Arylamine N-Acetyltransferase / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D017353:Gene Deletion; D005787:Gene Frequency; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics; D019512:Pancreatitis, Alcoholic / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D014357:Trypsin / Q000235:genetics; D014359:Trypsin Inhibitor, Kazal Pancreatic
chemical_list: D001191:Arylamine N-Acetyltransferase; D002352:Carrier Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005982:Glutathione Transferase; D008071:Lipoprotein Lipase; D016660:NAD(P)H Dehydrogenase (Quinone); D014357:Trypsin; D014359:Trypsin Inhibitor, Kazal Pancreatic; C505032:CFTR protein, human; C486642:SPINK1 protein, human; C447479:NQO1 protein, human; C478900:NAT2 protein, human; C413545:glutathione S-transferase T1; C489303:PRSS1 protein, human