Cytokine polymorphisms associated with clinical features and treatment outcome in type 1 autoimmune hepatitis
Gastroenterology, September 1999
Albert J. Czaja, Sharon Cookson, Patrizia K. Constantini, Michael Clare, James A. Underhill, Peter T. Donaldson
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.
|Readers by professional status||Count||As %|
|Readers by discipline||Count||As %|