Definition of polymorphisms and haplotypes in the interleukin-12B gene: association with IL-12 production but not with Crohn's disease.

Authors:
A Zwiers, D Seegers, R Heijmans, A Koch, J Hampe, S Nikolaus, A S Peña, S Schreiber, G Bouma
Year of publication:
2004
Volume:
5
Issue:
8
Issn:
1466-4879
Journal title abbreviated:
GENES IMMUN
Journal title long:
Genes and immunity
Impact factor:
2.472
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.