Presence of the IL-1RA allele 2 (IL1RN*2) is associated with enhanced IL-1beta production in vitro.
The genes of the interleukin-1 (IL-1) complex code for three proteins: IL-1alpha, IL-1beta and the IL-1 receptor antagonist (IL-1RA). Each of these genes is polymorphic and there is increasing evidence that certain alleles are associated with increased susceptibility to a given disease of inflammatory nature. In the IL-1beta gene there are two base-exchange polymorphisms in positions -511 and +3953, and IL-1RA gene has a penta-allelic polymorphic site in intron 2 containing variable numbers of an 86-bp tandem repeat sequence. As the IL-1beta/IL-1RA ratio may be critical in the regulation of inflammation, we examined whether there are allelic associations between these loci (thus suggesting co-ordinate regulation) and whether these have an effect on the in vitro production of IL-1beta. We found that the IL-1RA allele 2 (IL1RN*2) is associated with the presence of allele 2 of the IL-1beta gene (position -511) and with the absence of allele 2 of the IL-1beta gene (position +3953). Mononuclear cells from carriers of allele 2 (position -511) and non-carriers of allele 2 (position +3953) had a slight, but non-significant, elevated capacity to produce IL-1beta in vitro. However, IL-1RA allele 2 strongly increased in vitro production of IL-1beta, regardless of the presence or absence of these alleles. Taken together, these data suggest that the known allelisms in the IL-1beta gene are not major regulators of the in vitro IL-1beta production, but the IL-1RA allele 2 (or an unknown allele strongly associated with it) has a decisive role.
Santtila
S
S
Department of Microbiology and Immunology, University of Tampere Medical School, Finland.
Savinainen
K
K
Hurme
M
M
D000483:Alleles; D001782:Blood Donors; D002478:Cells, Cultured; D005838:Genotype; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D012795:Sialoglycoproteins / Q000235:genetics*
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins