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.
Zwiers
A
A
Laboratory of Immunogenetics, Vrije Universiteit Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
Seegers
D
D
Heijmans
R
R
Koch
A
A
Hampe
J
J
Nikolaus
S
S
Peña
A S
AS
Schreiber
S
S
Bouma
G
G
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