Association Analyses of Genetic Polymorphisms of GSTM1, GSTT1, NQO1, NAT2, LPL, PRSS1, PSTI, and CFTR With Chronic Alcoholic Pancreatitis in Japan
Katsuya Maruyama
From the Department of Internal Medicine, National Hospital Organization Kurihama Alcoholism Center (KM, AY, SM), Yokosuka, Japan; SRL, Inc. Center for Molecular Biology and Cytogenetics (SH), Hino, Tokyo, Japan; Department of Gastroenterology, Graduate School of Medicine, Nagoya University (SN), Nagoya, Japan; Department of Gastroenterological Surgery, Kumamoto University (MH), Kumamoto, Japan; Department of Gastroenterology and Hepatology, Kochi Medical School (IN), Kochi, Japan; and Department of Gastroenterology and Metabolism, University of Occupational and Environmental Health, Japan, School of Medicine (MO), Kitakyushu, Japan.
Search for more papers by this authorShoji Harada
From the Department of Internal Medicine, National Hospital Organization Kurihama Alcoholism Center (KM, AY, SM), Yokosuka, Japan; SRL, Inc. Center for Molecular Biology and Cytogenetics (SH), Hino, Tokyo, Japan; Department of Gastroenterology, Graduate School of Medicine, Nagoya University (SN), Nagoya, Japan; Department of Gastroenterological Surgery, Kumamoto University (MH), Kumamoto, Japan; Department of Gastroenterology and Hepatology, Kochi Medical School (IN), Kochi, Japan; and Department of Gastroenterology and Metabolism, University of Occupational and Environmental Health, Japan, School of Medicine (MO), Kitakyushu, Japan.
Search for more papers by this authorAkira Yokoyama
From the Department of Internal Medicine, National Hospital Organization Kurihama Alcoholism Center (KM, AY, SM), Yokosuka, Japan; SRL, Inc. Center for Molecular Biology and Cytogenetics (SH), Hino, Tokyo, Japan; Department of Gastroenterology, Graduate School of Medicine, Nagoya University (SN), Nagoya, Japan; Department of Gastroenterological Surgery, Kumamoto University (MH), Kumamoto, Japan; Department of Gastroenterology and Hepatology, Kochi Medical School (IN), Kochi, Japan; and Department of Gastroenterology and Metabolism, University of Occupational and Environmental Health, Japan, School of Medicine (MO), Kitakyushu, Japan.
Search for more papers by this authorSatoshi Mizukami
From the Department of Internal Medicine, National Hospital Organization Kurihama Alcoholism Center (KM, AY, SM), Yokosuka, Japan; SRL, Inc. Center for Molecular Biology and Cytogenetics (SH), Hino, Tokyo, Japan; Department of Gastroenterology, Graduate School of Medicine, Nagoya University (SN), Nagoya, Japan; Department of Gastroenterological Surgery, Kumamoto University (MH), Kumamoto, Japan; Department of Gastroenterology and Hepatology, Kochi Medical School (IN), Kochi, Japan; and Department of Gastroenterology and Metabolism, University of Occupational and Environmental Health, Japan, School of Medicine (MO), Kitakyushu, Japan.
Search for more papers by this authorSatoru Naruse
From the Department of Internal Medicine, National Hospital Organization Kurihama Alcoholism Center (KM, AY, SM), Yokosuka, Japan; SRL, Inc. Center for Molecular Biology and Cytogenetics (SH), Hino, Tokyo, Japan; Department of Gastroenterology, Graduate School of Medicine, Nagoya University (SN), Nagoya, Japan; Department of Gastroenterological Surgery, Kumamoto University (MH), Kumamoto, Japan; Department of Gastroenterology and Hepatology, Kochi Medical School (IN), Kochi, Japan; and Department of Gastroenterology and Metabolism, University of Occupational and Environmental Health, Japan, School of Medicine (MO), Kitakyushu, Japan.
Search for more papers by this authorMasahiko Hirota
From the Department of Internal Medicine, National Hospital Organization Kurihama Alcoholism Center (KM, AY, SM), Yokosuka, Japan; SRL, Inc. Center for Molecular Biology and Cytogenetics (SH), Hino, Tokyo, Japan; Department of Gastroenterology, Graduate School of Medicine, Nagoya University (SN), Nagoya, Japan; Department of Gastroenterological Surgery, Kumamoto University (MH), Kumamoto, Japan; Department of Gastroenterology and Hepatology, Kochi Medical School (IN), Kochi, Japan; and Department of Gastroenterology and Metabolism, University of Occupational and Environmental Health, Japan, School of Medicine (MO), Kitakyushu, Japan.
Search for more papers by this authorIsao Nishimori
From the Department of Internal Medicine, National Hospital Organization Kurihama Alcoholism Center (KM, AY, SM), Yokosuka, Japan; SRL, Inc. Center for Molecular Biology and Cytogenetics (SH), Hino, Tokyo, Japan; Department of Gastroenterology, Graduate School of Medicine, Nagoya University (SN), Nagoya, Japan; Department of Gastroenterological Surgery, Kumamoto University (MH), Kumamoto, Japan; Department of Gastroenterology and Hepatology, Kochi Medical School (IN), Kochi, Japan; and Department of Gastroenterology and Metabolism, University of Occupational and Environmental Health, Japan, School of Medicine (MO), Kitakyushu, Japan.
Search for more papers by this authorMakoto Otsuki
From the Department of Internal Medicine, National Hospital Organization Kurihama Alcoholism Center (KM, AY, SM), Yokosuka, Japan; SRL, Inc. Center for Molecular Biology and Cytogenetics (SH), Hino, Tokyo, Japan; Department of Gastroenterology, Graduate School of Medicine, Nagoya University (SN), Nagoya, Japan; Department of Gastroenterological Surgery, Kumamoto University (MH), Kumamoto, Japan; Department of Gastroenterology and Hepatology, Kochi Medical School (IN), Kochi, Japan; and Department of Gastroenterology and Metabolism, University of Occupational and Environmental Health, Japan, School of Medicine (MO), Kitakyushu, Japan.
Search for more papers by this authorKatsuya Maruyama
From the Department of Internal Medicine, National Hospital Organization Kurihama Alcoholism Center (KM, AY, SM), Yokosuka, Japan; SRL, Inc. Center for Molecular Biology and Cytogenetics (SH), Hino, Tokyo, Japan; Department of Gastroenterology, Graduate School of Medicine, Nagoya University (SN), Nagoya, Japan; Department of Gastroenterological Surgery, Kumamoto University (MH), Kumamoto, Japan; Department of Gastroenterology and Hepatology, Kochi Medical School (IN), Kochi, Japan; and Department of Gastroenterology and Metabolism, University of Occupational and Environmental Health, Japan, School of Medicine (MO), Kitakyushu, Japan.
Search for more papers by this authorShoji Harada
From the Department of Internal Medicine, National Hospital Organization Kurihama Alcoholism Center (KM, AY, SM), Yokosuka, Japan; SRL, Inc. Center for Molecular Biology and Cytogenetics (SH), Hino, Tokyo, Japan; Department of Gastroenterology, Graduate School of Medicine, Nagoya University (SN), Nagoya, Japan; Department of Gastroenterological Surgery, Kumamoto University (MH), Kumamoto, Japan; Department of Gastroenterology and Hepatology, Kochi Medical School (IN), Kochi, Japan; and Department of Gastroenterology and Metabolism, University of Occupational and Environmental Health, Japan, School of Medicine (MO), Kitakyushu, Japan.
Search for more papers by this authorAkira Yokoyama
From the Department of Internal Medicine, National Hospital Organization Kurihama Alcoholism Center (KM, AY, SM), Yokosuka, Japan; SRL, Inc. Center for Molecular Biology and Cytogenetics (SH), Hino, Tokyo, Japan; Department of Gastroenterology, Graduate School of Medicine, Nagoya University (SN), Nagoya, Japan; Department of Gastroenterological Surgery, Kumamoto University (MH), Kumamoto, Japan; Department of Gastroenterology and Hepatology, Kochi Medical School (IN), Kochi, Japan; and Department of Gastroenterology and Metabolism, University of Occupational and Environmental Health, Japan, School of Medicine (MO), Kitakyushu, Japan.
Search for more papers by this authorSatoshi Mizukami
From the Department of Internal Medicine, National Hospital Organization Kurihama Alcoholism Center (KM, AY, SM), Yokosuka, Japan; SRL, Inc. Center for Molecular Biology and Cytogenetics (SH), Hino, Tokyo, Japan; Department of Gastroenterology, Graduate School of Medicine, Nagoya University (SN), Nagoya, Japan; Department of Gastroenterological Surgery, Kumamoto University (MH), Kumamoto, Japan; Department of Gastroenterology and Hepatology, Kochi Medical School (IN), Kochi, Japan; and Department of Gastroenterology and Metabolism, University of Occupational and Environmental Health, Japan, School of Medicine (MO), Kitakyushu, Japan.
Search for more papers by this authorSatoru Naruse
From the Department of Internal Medicine, National Hospital Organization Kurihama Alcoholism Center (KM, AY, SM), Yokosuka, Japan; SRL, Inc. Center for Molecular Biology and Cytogenetics (SH), Hino, Tokyo, Japan; Department of Gastroenterology, Graduate School of Medicine, Nagoya University (SN), Nagoya, Japan; Department of Gastroenterological Surgery, Kumamoto University (MH), Kumamoto, Japan; Department of Gastroenterology and Hepatology, Kochi Medical School (IN), Kochi, Japan; and Department of Gastroenterology and Metabolism, University of Occupational and Environmental Health, Japan, School of Medicine (MO), Kitakyushu, Japan.
Search for more papers by this authorMasahiko Hirota
From the Department of Internal Medicine, National Hospital Organization Kurihama Alcoholism Center (KM, AY, SM), Yokosuka, Japan; SRL, Inc. Center for Molecular Biology and Cytogenetics (SH), Hino, Tokyo, Japan; Department of Gastroenterology, Graduate School of Medicine, Nagoya University (SN), Nagoya, Japan; Department of Gastroenterological Surgery, Kumamoto University (MH), Kumamoto, Japan; Department of Gastroenterology and Hepatology, Kochi Medical School (IN), Kochi, Japan; and Department of Gastroenterology and Metabolism, University of Occupational and Environmental Health, Japan, School of Medicine (MO), Kitakyushu, Japan.
Search for more papers by this authorIsao Nishimori
From the Department of Internal Medicine, National Hospital Organization Kurihama Alcoholism Center (KM, AY, SM), Yokosuka, Japan; SRL, Inc. Center for Molecular Biology and Cytogenetics (SH), Hino, Tokyo, Japan; Department of Gastroenterology, Graduate School of Medicine, Nagoya University (SN), Nagoya, Japan; Department of Gastroenterological Surgery, Kumamoto University (MH), Kumamoto, Japan; Department of Gastroenterology and Hepatology, Kochi Medical School (IN), Kochi, Japan; and Department of Gastroenterology and Metabolism, University of Occupational and Environmental Health, Japan, School of Medicine (MO), Kitakyushu, Japan.
Search for more papers by this authorMakoto Otsuki
From the Department of Internal Medicine, National Hospital Organization Kurihama Alcoholism Center (KM, AY, SM), Yokosuka, Japan; SRL, Inc. Center for Molecular Biology and Cytogenetics (SH), Hino, Tokyo, Japan; Department of Gastroenterology, Graduate School of Medicine, Nagoya University (SN), Nagoya, Japan; Department of Gastroenterological Surgery, Kumamoto University (MH), Kumamoto, Japan; Department of Gastroenterology and Hepatology, Kochi Medical School (IN), Kochi, Japan; and Department of Gastroenterology and Metabolism, University of Occupational and Environmental Health, Japan, School of Medicine (MO), Kitakyushu, Japan.
Search for more papers by this authorAbstract
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.
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