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.
引用
收藏
页数:7
相关论文
共 34 条
[1]   Genetic polymorphisms of the UDP-glucuronosyltransferase 1A7 gene and irinotecan toxicity in Japanese cancer patients [J].
Ando, M ;
Ando, Y ;
Sekido, Y ;
Ando, M ;
Shimokata, K ;
Hasegawa, Y .
JAPANESE JOURNAL OF CANCER RESEARCH, 2002, 93 (05) :591-597
[2]   Relation between mutations of the cystic fibrosis gene and idiopathic pancreatitis [J].
Cohn, JA ;
Friedman, KJ ;
Noone, PG ;
Knowles, MR ;
Silverman, LM ;
Jowell, PS .
NEW ENGLAND JOURNAL OF MEDICINE, 1998, 339 (10) :653-658
[3]   Mutations in serine protease inhibitor Kazal type 1 are strongly associated with chronic pancreatitis [J].
Drenth, JPH ;
te Morsche, R ;
Jansen, JBMJ .
GUT, 2002, 50 (05) :687-692
[4]   OCCUPATION AND PANCREATIC-CANCER RISK IN LOUISIANA [J].
FALK, RT ;
PICKLE, LW ;
FONTHAM, ET ;
CORREA, P ;
MORSE, A ;
CHEN, V ;
FRAUMENI, JJ .
AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, 1990, 18 (05) :565-576
[5]   INDUCTION OF DRUG-METABOLIZING-ENZYMES IN HUMAN PANCREATIC-CANCER AND CHRONIC-PANCREATITIS [J].
FOSTER, JR ;
IDLE, JR ;
HARDWICK, JP ;
BARS, R ;
SCOTT, P ;
BRAGANZA, JM .
JOURNAL OF PATHOLOGY, 1993, 169 (04) :457-463
[6]   Structural heterogeneity at the UDP-glucuronosyltransferase 1 locus:: functional consequences of three novel missense mutations in the human UGT1A7 gene [J].
Guillemette, C ;
Ritter, JK ;
Auyeung, DJ ;
Kessler, FK ;
Housman, DE .
PHARMACOGENETICS, 2000, 10 (07) :629-644
[7]   Identification and functional characterization of UDP-glucuronosyltransferases UGT1A8*1, UGT1A8*2 and UGT1A8*3 [J].
Huang, YH ;
Galijatovic, A ;
Nguyen, N ;
Geske, D ;
Beaton, D ;
Green, J ;
Green, M ;
Peters, WH ;
Tukey, RH .
PHARMACOGENETICS, 2002, 12 (04) :287-297
[8]   Functional characterization of wild-type and variant (T202I and M59I) human UDP-glucuronosyltransferase 1A10 [J].
Jinno, H ;
Saeki, M ;
Tanaka-Kagawa, T ;
Hanioka, N ;
Saito, Y ;
Ozawa, S ;
Ando, M ;
Shirao, K ;
Minami, H ;
Ohtsu, A ;
Yoshida, T ;
Saijo, N ;
Sawada, JI .
DRUG METABOLISM AND DISPOSITION, 2003, 31 (05) :528-532
[9]   UDP-glucuronosyltransferases [J].
King, CD ;
Rios, GR ;
Green, MD ;
Tephly, TR .
CURRENT DRUG METABOLISM, 2000, 1 (02) :143-161
[10]   Frequent co-occurrence of the TATA box mutation associated with Gilbert's syndrome (UGT1A1*28) with other polymorphisms of the UDP-glucuronosyltransferase-1 locus (UGT1A6*2 and UGT1A7*3) in Caucasians and Egyptians [J].
Köhle, C ;
Möhrle, B ;
Münzel, PA ;
Schwab, M ;
Wernet, D ;
Badary, OA ;
Bock, KW .
BIOCHEMICAL PHARMACOLOGY, 2003, 65 (09) :1521-1527