Frequency and nature of cytokine gene polymorphisms in type 1 autoimmune hepatitis

✍ Scribed by Sharon Cookson; Patrizia K. Constantini; Michael Clare; James A. Underhill; Will Bernal; Albert J. Czaja; Peter T. Donaldson

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 90 KB
• Volume: 30
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.510300412

✦ Synopsis

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-␣ (TNF-␣) 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. (HEPATOLOGY 1999;30:851-856.