Background: An imbalance between the proinflammatory cytokine interleukin 1 beta (IL-1 beta) and the anti-inflammatory cytokine IL-1 receptor antagonist (IL-1ra) has been postulated as a pathogenic factor in inflammatory bowel disease (IBD).
Aims: To study allelic frequencies of novel polymorphisms in the genes for IL-1 beta and IL-1ra in patients with IBD and to assess the relation between ex vivo cytokine production and allelic variants of the IL-1 beta and IL-1ra genes.
Subjects: Two hundred and seventy healthy controls, 74 patients with ulcerative colitis (UC), 72 with Crohn's disease (CD), 40 with primary sclerosing cholangitis for the allelic frequencies, and 60 healthy individuals for the ex vivo stimulation test.
Methods: Genotyping was performed by polymerase chain reaction and subsequent cleavage with specific endonucleases (Mwo1, MspAI1, Alu1, Taq1, BsoF1) for five novel restriction fragment length polymorphisms (RFLPs) in the genes for IL-1ra and IL-1 beta.
Results: No significant differences were found in the allelic frequencies or allele carriage rates of the markers in the IL-1 beta and IL-1ra genes between CD, UC, and healthy controls. No association between the genetic markers and cytokine production levels was observed. Patients with UC carried the combination of both the infrequent allele of the Taq1 RFLP and the Mwo1 RFLP significantly more frequently (35.2% in UC versus 71.1% in controls).
Conclusions: UC is associated with carriage of both infrequent alleles of the Taq1 and Mwo1 RFLPs. However, it could not be confirmed whether the association reflects a pathogenic mechanism underlying UC.