Polymorphisms of UDP-glucuronosyltransferase 1A7 are not involved in pancreatic diseases -: art. no. e62

被引:30
作者
Verlaan, M
Drenth, JPH
Truninger, K
Koudova, M
Schulz, HU
Bargetzi, M
Künzli, B
Friess, H
Cerny, M
Kage, A
Landt, O
Morsche, RHMT
Rosendahl, J
Luck, W
Nickel, R
Halangk, J
Becker, M
Macek, M
Jansen, JBMJ
Witt, H
机构
[1] Charite, Dept Gastroenterol & Hepatol, D-13353 Berlin, Germany
[2] Radboud Univ Nijmegen Med Ctr, Dept Med, Div Gastroenterol & Hepatol, Nijmegen, Netherlands
[3] Kantonspital, Div Gastroenterol, Aarau, Switzerland
[4] Kantonspital, Ctr Oncol Haematol, Aarau, Switzerland
[5] Univ Hosp Motol, Cyst Fibrosis Ctr, Inst Biol & Med Genet, Prague, Czech Republic
[6] Charles Univ Prague, Sch Med 2, Prague, Czech Republic
[7] Otto von Guericke Univ, Dept Surg, Magdeburg, Germany
[8] Heidelberg Univ, Dept Gen Surg, Heidelberg, Germany
[9] Charles Univ Prague, Dept Neonatol, Clin Obstet & Gynaecol, Prague, Czech Republic
[10] Univ Med Berlin, Charite, Dept Lab Med & Pathobiochem, Berlin, Germany
[11] Charite, Dept Paediat, Berlin, Germany
[12] TIB MOLBIOL, Berlin, Germany
关键词
D O I
10.1136/jmg.2005.032599
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Background: Xenobiotic mediated cellular injury is thought to play a major role in the pathogenesis of pancreatic diseases. Genetic variations that reduce the expression or activity of detoxifying phase II biotransformation enzymes such as the UDP-glucuronosyltransferases might be important in this respect. Recently, a UGT1A7 low detoxification activity allele, UGT1A7*3, has been linked to pancreatic cancer and alcoholic chronic pancreatitis. Objective: To investigate whether UGT1A7 polymorphisms contribute to the risk of pancreatitis and pancreatic cancer. Methods: Genetic polymorphisms in the UGT1A7 gene were assessed in a large cohort of patients with different types of pancreatitis and pancreatic cancer originating from the Czech Republic (n = 93), Germany ( n = 638), Netherlands ( n = 136), and Switzerland ( n = 106), and in healthy ( n = 1409) and alcoholic ( n = 123) controls from the same populations. Polymorphisms were determined by melting curve analysis using fluorescence resonance energy transfer probes. In addition, 229 Dutch subjects were analysed by restriction fragment length polymorphism. Results: The frequencies of UGT1A7 genotypes did not differ between patients with acute or chronic pancreatitis or pancreatic adenocarcinoma and alcoholic and healthy controls. Conclusions: The data suggest that, in contrast to earlier studies, UGT1A7 polymorphisms do not predispose patients to the development of pancreatic cancer and pancreatitis.
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页数:7
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共 34 条
[21]   MEDICAL PROGRESS - CHRONIC-PANCREATITIS [J].
STEER, ML ;
WAXMAN, I ;
FREEDMAN, S .
NEW ENGLAND JOURNAL OF MEDICINE, 1995, 332 (22) :1482-1490
[22]   Polymorphisms of the human UDP-glucuronosyltransferase (UGT) 1A7 gene in colorectal cancer [J].
Strassburg, CP ;
Vogel, A ;
Kneip, S ;
Tukey, RH ;
Manns, MP .
GUT, 2002, 50 (06) :851-856
[23]   Expression of the UDP-glucuronosyltransferase 1A locus in human colon - Identification and characterization of the novel extrahepatic UGT1A8 [J].
Strassburg, CP ;
Manns, MP ;
Tukey, RH .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (15) :8719-8726
[24]   Genetic multiplicity of the human UDP-glucuronosyltransferases and regulation in the gastrointestinal tract [J].
Tukey, RH ;
Strassburg, CP .
MOLECULAR PHARMACOLOGY, 2001, 59 (03) :405-414
[25]   Human UDP-glucuronosyltransferases: Metabolism, expression, and disease [J].
Tukey, RH ;
Strassburg, CP .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 2000, 40 :581-616
[26]   Novel functional polymorphisms in the UGT1A7 and UGT1A9 glucuronidating enzymes in Caucasian and African-American subjects and their impact on the metabolism of 7-ethyl-10-hydroxycamptothecin and flavopiridol anticancer drugs [J].
Villeneuve, L ;
Girard, H ;
Fortier, LC ;
Gagné, JF ;
Guillemette, C .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2003, 307 (01) :117-128
[27]   Polymorphisms of the carcinogen detoxifying UDP-glucuronosyltransferase UGT1A7 in proximal digestive tract cancer [J].
Vogel, A ;
Ockenga, J ;
Ehmer, U ;
Barut, A ;
Kramer, FJ ;
Tukey, RH ;
Manns, MP ;
Strassburg, CP .
ZEITSCHRIFT FUR GASTROENTEROLOGIE, 2002, 40 (07) :497-502
[28]   Genetic link of hepatocellular carcinoma with polymorphisms of the UDP-glucuronosyltransferase UGTIA7 gene [J].
Vogel, A ;
Kneip, S ;
Barut, A ;
Ehmer, U ;
Tukey, RH ;
Manns, MP ;
Strassburg, CP .
GASTROENTEROLOGY, 2001, 121 (05) :1136-1144
[29]   Up-regulation of cytochrome P450 1A2, 2C9, and 2E1 in chronic pancreatitis [J].
Wacke, R ;
Kirchner, A ;
Prall, F ;
Nizze, H ;
Schmidt, W ;
Fischer, U ;
Nitschke, FP ;
Adam, U ;
Fritz, P ;
Belloc, C ;
Drewelow, B .
PANCREAS, 1998, 16 (04) :521-528
[30]   Xenobiotic metabolism, oxidant stress and chronic pancreatitis - Focus on glutathione [J].
Wallig, MA .
DIGESTION, 1998, 59 :13-24