Autoimmune hepatitis in Brazilian patients is not linked to tumor necrosis factor α polymorphisms at position-308

被引:30
作者
Bittencourt, PL
Palácios, SA
Cançado, ELR
Porta, G
Drigo, S
Carrilho, FJ
Laudanna, AA
Kalil, J
Goldberg, AC
机构
[1] Univ Sao Paulo, Sch Med, Dept Gastroenterol, Sao Paulo, Brazil
[2] Univ Sao Paulo, Sch Med, Childrens Inst, Liver Unit, Sao Paulo, Brazil
[3] Univ Sao Paulo, Sch Med, Immunol Lab, Inst Heart, Sao Paulo, Brazil
[4] Howard Hughes Med Inst, Bethesda, MD 20815 USA
基金
巴西圣保罗研究基金会;
关键词
tumor necrosis factor alpha gene polymorphisms; tumor necrosis factor alpha; autoimmune hepatitis; HLA-DR antigens; genetic susceptibility;
D O I
10.1016/S0168-8278(01)00072-1
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background/Aims: Susceptibility to autoimmune hepatitis (AIH) has been linked to different HLA-DR antigens, Recently, AIH type 1 was associated with polymorphisms in the tumor necrosis factor alpha gene promotes (TNFA) at position -308. In this respect, the frequency of the TNFA*2 allele, in linkage disequilibrium with HLA-DRB1*0301, was shown to be significantly increased in whites with AIH type 1. The aim of this study was to assess the role of TNFA alleles in conferring susceptibility to AIH, studying a population where the disease is not primarily associated with HLA-DRB1*03. Methods: The determination of HLA-DRB1 and TNFA alleles was performed in 92 patients with ALH type 1, 29 subjects with AIH type 2 and 53 healthy controls by polymerase chain reaction-based techniques. Results: The distribution of TNFA alleles was similar in patients with AIH types 1 and 2, when compared with controls. In addition, the TNFA*2 allele was identified in patients carrying HLA-DR antigens other than HLA-DRB1*03. Interestingly, higher gammaglobulin levels were observed in TNFA*2 positive patients. Conclusions: Our data indicate that susceptibility to AIH remains primarily linked to the HLA-DRB1 locus, and suggest that the association of AIH with TNFA*2 previously observed in whites might be secondary to a linkage disequilibrium with MLA-DRB1*0301, (C) 2001 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.
引用
收藏
页码:24 / 28
页数:5
相关论文
共 36 条
[1]   CHARACTERIZATION OF THE LIVER CYTOSOL ANTIGEN TYPE-1 REACTING WITH AUTOANTIBODIES IN CHRONIC ACTIVE HEPATITIS [J].
ABUAF, N ;
JOHANET, C ;
CHRETIEN, P ;
MARTINI, E ;
SOULIER, E ;
LAPERCHE, S ;
HOMBERG, JC .
HEPATOLOGY, 1992, 16 (04) :892-898
[2]   International Autoimmune Hepatitis Group Report:: review of criteria for diagnosis of autoimmune hepatitis [J].
Alvarez, E ;
Berg, PA ;
Bianchi, FB ;
Bianchi, L ;
Burroughs, AK ;
Cancado, EL ;
Chapman, RW ;
Cooksley, WGE ;
Czaja, AJ ;
Desmet, VJ ;
Donaldson, RT ;
Eddleston, ALWF ;
Fainboim, L ;
Heathcote, J ;
Homberg, JC ;
Hoofnagle, JH ;
Kakumu, S ;
Krawitt, EL ;
Mackay, IR ;
MacSween, RNM ;
Maddrey, WC ;
Manns, MP ;
McFarlane, IG ;
zum Büschenfelde, KHM ;
Mieli-Vergani, G ;
Nakanuma, Y ;
Nishioka, M ;
Penner, E ;
Porta, G ;
Portmann, BC ;
Reed, WD ;
Rodes, J ;
Schalm, SW ;
Scheuer, PJ ;
Schrumpf, E ;
Seki, T ;
Toda, G ;
Tsuji, T ;
Tygstrup, N ;
Vergani, D ;
Zeniya, M .
JOURNAL OF HEPATOLOGY, 1999, 31 (05) :929-938
[3]  
Beutler BA, 1999, J RHEUMATOL, V26, P16
[4]   Different HLA profiles confer susceptibility to autoimmune hepatitis type 1 and 2 [J].
Bittencourt, PL ;
Goldberg, AC ;
Cançado, ELR ;
Porta, G ;
Laudanna, AA ;
Kalil, J .
AMERICAN JOURNAL OF GASTROENTEROLOGY, 1998, 93 (08) :1394-1395
[5]  
Bittencourt PL, 1999, AM J GASTROENTEROL, V94, P1906
[6]  
Cancado ELR, 1996, HEPATOLOGY, V23, P1098
[7]  
Cançado ELR, 2000, FALK SYMP, V114, P82
[8]   Frequency and nature of cytokine gene polymorphisms in type 1 autoimmune hepatitis [J].
Cookson, S ;
Constantini, PK ;
Clare, M ;
Underhill, JA ;
Bernal, W ;
Czaja, AJ ;
Donaldson, PT .
HEPATOLOGY, 1999, 30 (04) :851-856
[9]  
CORDONERFRANCH P, 1989, CLIN EXP IMMUNOL, V75, P354
[10]  
Czaja AJ, 1997, HEPATOLOGY, V25, P317