Cytokine polymorphisms associated with clinical features and treatment outcome in type 1 autoimmune hepatitis

Background & Aims: Polymorphisms that control cytokine production can affec t immunoregulation. The frequency and consequences of these polymorphisms i n type 1 autoimmune hepatitis were determined. Methods: DNA samples from 15 5 patients and 102 ethnically similar normal individuals were assessed by p olymerase chain reaction for polymorphisms of 4 different cytokine-producin g genes. Results: Only genotypes associated with the guanine to adenine sub stitution at position -308 of the tumor necrosis factor gene occurred more commonly in patients than in normal subjects (56% vs. 26%; P < 0.001). Pati ents with this polymorphism had the HLA DRB1*0301 allele (81% vs. 10%; P < 0.000001) and A1-B8-DRB1*0301 (66% vs. 0%; P < 0.000001) phenotype more fre quently and HLA DRB1*04 alleles less often (24% vs. 67%; P < 0.000001). The y also entered remission less commonly (56% vs. 78%; P = 0.01), had treatme nt failure more often (20% vs. 7%; P = 0.03), and developed cirrhosis more frequently (40% vs. 19%; P = 0.05). These latter differences, however, were not statistically significant by adjusted P value. Conclusions: A polymorp hism of the tumor necrosis factor gene occurs more commonly in patients wit h type 1 autoimmune hepatitis than in normal subjects; it is associated wit h a poorer response to corticosteroids. The polymorphism may be inherited a s part of the extended A1-B8-DRB1*0301 haplotype and may affect both diseas e expression and behavior.