Cytokine polymorphisms associated with clinical features and treatment outcome in type 1 autoimmune hepatitis.
OBJECTIVE
Polymorphisms that control cytokine production can affect immunoregulation. The frequency and consequences of these polymorphisms in type 1 autoimmune hepatitis were determined.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Czaja
A J
AJ
Division of Gastroenterology and Hepatology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA. czaja.albert@mayo.edu
Cookson
S
S
Constantini
P K
PK
Clare
M
M
Underhill
J A
JA
Donaldson
P T
PT
D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000032:analysis; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D004247:DNA / Q000032:analysis; D005260:Female; D005838:Genotype; D005938:Glucocorticoids / Q000627:therapeutic use; D006681:HLA-D Antigens / Q000235:genetics; D019693:Hepatitis, Autoimmune / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011241:Prednisone / Q000627:therapeutic use; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D001323:Autoantibodies; D016207:Cytokines; D005938:Glucocorticoids; D006681:HLA-D Antigens; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D004247:DNA; D011241:Prednisone