Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Cookson, S; Constantini, PK; Clare, M; Underhill, JA; Bernal, W; Czaja, AJ; Donaldson, PT.
Frequency and nature of cytokine gene polymorphisms in type 1 autoimmune hepatitis.
Hepatology. 1999; 30(4):851-856
Doi: 10.1002/hep.510300412
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- Co-Autor*innen der Med Uni Graz
- Constantini-Kump Patrizia
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- Abstract:
- Genetic involvement in type 1 autoimmune hepatitis (AIH) is indicated by a marked female preponderance and strong, well-established, human leukocyte antigen (HLA) associations. These associations, however, are not universal and a number of genes outside the major histocompatibility complex may also play a role in susceptibility to type 1 AIH. Prime candidates at present are those polymorphic genes encoding the proinflammatory and immunoregulatory cytokines. The aim of this study was to investigate, for the first time, 2 members of the interleukin-1 (IL-1) family (IL-1B and IL-1RN), 3 polymorphic sites in the interleukin-10 (IL-10) gene promoter (positions -1082, -819, and -592), and 2 polymorphisms in the tumor necrosis factor-alpha (TNF-alpha) promoter (positions -308 and -238) in type 1 AIH. The study was performed on 2 independently collected DNA banks, each with appropriate controls, and throughout the analysis associations described in the first set were confirmed in the second set. Standard polymerase chain reaction (PCR)-based genotyping techniques were used. Overall there were no significant differences in the distributions of the IL-1B and IL-10 alleles, genotypes, or haplotypes in either study set. In contrast we report a significant association between type 1 AIH and TNF*2 (first set: 34% of controls vs. 49% of patients, Pc =.014 and second set: 26% vs. 56%, P =.00008). However, TNF*2 is found in strong linkage disequilibrium with the HLA A1-B8-DR3 haplotype and stratification analysis indicates that the association with TNF*2 is interdependent with HLA DRB1*0301. This is an indication that there is more than one susceptibility allele for type 1 AIH on chromosome 6p21.3.
- Find related publications in this database (using NLM MeSH Indexing)
- Adolescent -
- Adult -
- Aged -
- Alleles -
- Cytokines - genetics
- Female -
- Genetic Linkage -
- Genetic Predisposition to Disease - genetics
- Genotype -
- HLA-B8 Antigen - genetics
- Hepatitis, Autoimmune - genetics
- Humans -
- Interleukin 1 Receptor Antagonist Protein -
- Interleukin-1 - genetics
- Interleukin-10 - genetics
- Male -
- Middle Aged -
- Polymorphism, Genetic - genetics
- Promoter Regions, Genetic - genetics
- Reference Values -
- Sialoglycoproteins - genetics
- Tumor Necrosis Factor-alpha - genetics