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Gastroenterology. 1999 Sep;117(3):645-52.

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

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Division of Gastroenterology and Hepatology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA.



Polymorphisms that control cytokine production can affect immunoregulation. The frequency and consequences of these polymorphisms in type 1 autoimmune hepatitis were determined.


DNA samples from 155 patients and 102 ethnically similar normal individuals were assessed by polymerase chain reaction for polymorphisms of 4 different cytokine-producing genes.


Only genotypes associated with the guanine to adenine substitution at position -308 of the tumor necrosis factor gene occurred more commonly in patients than in normal subjects (56% vs. 26%; P < 0.001). Patients 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 frequently and HLA DRB1*04 alleles less often (24% vs. 67%; P < 0.000001). They also entered remission less commonly (56% vs. 78%; P = 0.01), had treatment 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.


A polymorphism of the tumor necrosis factor gene occurs more commonly in patients with type 1 autoimmune hepatitis than in normal subjects; it is associated with a poorer response to corticosteroids. The polymorphism may be inherited as part of the extended A1-B8-DRB1*0301 haplotype and may affect both disease expression and behavior.

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