Association of HLA-DR genotypes and IL-1ra gene polymorphism with treatment failure of budesonide and disease patterns in Crohn's disease.
OBJECTIVE
Associations between HLA-DR genotypes and susceptibility to Crohn's disease (CD) have been reported. However, it is not known whether certain HLA-DR genotypes or IL-1ra gene polymorphism are associated with responsiveness to treatment or different clinical patterns of disease.


METHODS
In a large, randomized, controlled multicentre trial, 318 patients with CD were treated with daily doses of 6, 9 or 18 mg budesonide. Patients were stratified into two groups: patients without steroid pretreatment and with active CD (CDAI > 150) and patients with conventional steroid pretreatment of < or= 30 mg prednisolone per day, which was replaced by oral budesonide within 3 weeks.


METHODS
The HLA-DRB1 genotypes 1-16 and the IL-1ra gene polymorphism were examined for an association with budesonide treatment failure.


RESULTS
Only HLA-DR 8 was associated with treatment failure of budesonide. HLA-DR 8 is not very common. Only 17/243 patients who could be evaluated expressed this genotype, and 13 of these 17 patients did not respond to budesonide (P < 0.00067). Neither the other HLA-DR genotypes nor the IL-1ra gene polymorphism had an influence on treatment outcome of budesonide therapy. No significant association of fistulas, perianal disease, need for bowel resections, and disease localization with certain HLA-DRB1 genotypes or the IL-1ra gene polymorphism were found.


CONCLUSIONS
This is the first description of an association of a certain HLA-DR genotype (HLA-DR 8) with treatment failure in inflammatory bowel disease (IBD).
Gelbmann
C M
CM
Department of Internal Medicine I, University of Regensburg, Germany. cornelia.gelbmann@klinik.uni-regensburg.de
Rogler
G
G
Gierend
M
M
Gross
V
V
Schölmerich
J
J
Andus
T
T
D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D019819:Budesonide / Q000627:therapeutic use*; D003424:Crohn Disease / Q000188:drug therapy* / Q000235:genetics*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics*; D059810:HLA-DR Serological Subtypes; D059811:HLA-DRB1 Chains; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012795:Sialoglycoproteins / Q000235:genetics*; D017211:Treatment Failure
D000893:Anti-Inflammatory Agents; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C041559:HLA-DR8 antigen; D059811:HLA-DRB1 Chains; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D012795:Sialoglycoproteins; D019819:Budesonide