1. ¹Laboratory of Immunogenetics, Vrije Universiteit Medical Center, Amsterdam, The Netherlands
2. ²Department of Gastroenterology, University of Kiel, Germany

Correspondence: Dr G Bouma, Laboratory of Immunogenetics, Vrije Universiteit Medical Center, Van der Boechorststraat 7, Room J393, 1081 BT Amsterdam, The Netherlands. E-mail: gbouma@niaid.nih.gov

Received 26 May 2004; Accepted 26 July 2004; Published online 14 October 2004.

Abstract

Interleukin-12 (IL-12) is a key cytokine for the induction of Th1 immune responses. Recently, functional polymorphisms in IL-12p40 (IL12B) were found to be associated with susceptibility to several autoimmune diseases. Similarly, variation in IL12B might be involved in susceptibility to Crohn's disease (CD), a chronic inflammatory bowel disorder associated with high IL-12 expression. We searched for additional polymorphism in IL12B and genotyped a large cohort of CD patients. Differential in vitro secretors of IL-12 were tested for polymorphism. Polymorphisms were analyzed using the intrafamilial transmission disequilibrium test (TDT) and by case–control analysis. A novel polymorphism was strongly associated with differential expression of IL-12. However, no association with susceptibility to CD was seen for this and other polymorphisms. The high level of conservation is consistent with the key regulatory role of IL-12. The lack of association with IL12B makes it unlikely that this gene is directly involved in the susceptibility to CD.