Definition of polymorphisms and haplotypes in the interleukin-12B gene: association with IL-12 production but not with Crohn's disease.
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.
Laboratory of Immunogenetics, Vrije Universiteit Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
A
A
Zwiers
D
D
Seegers
R
R
Heijmans
A
A
Koch
J
J
Hampe
S
S
Nikolaus
A S
AS
Peña
S
S
Schreiber
G
G
Bouma
D001483:Base Sequence; D016022:Case-Control Studies; D003424:Crohn Disease / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics*; D053762:Interleukin-12 Subunit p40; D015810:Linkage Disequilibrium; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic
C500879:IL12B protein, human; D053762:Interleukin-12 Subunit p40; D018664:Interleukin-12