Santtila S, Savinainen K, Hurme M
Department of Microbiology and Immunology, University of Tampere Medical School, Finland.
Scand J Immunol. 1998 Mar;47(3):195-8. doi: 10.1046/j.1365-3083.1998.00300.x.
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.
白细胞介素 -1（IL -1）复合体的基因编码三种蛋白质：IL -1α、IL -1β和IL -1受体拮抗剂（IL -1RA）。这些基因中的每一个都具有多态性，并且越来越多的证据表明某些等位基因与对特定炎症性疾病易感性增加有关。在IL -1β基因的 -511和 +3953位置存在两个碱基交换多态性，并且IL -1RA基因在第2内含子中有一个五等位基因多态性位点，其中包含可变数量的86个碱基对的串联重复序列。由于IL -1β/IL -1RA比值在炎症调节中可能至关重要，我们研究了这些基因座之间是否存在等位基因关联（从而提示协同调节）以及这些关联是否对IL -1β的体外产生有影响。我们发现IL -1RA等位基因2（IL1RN*2）与IL -1β基因（-511位置）的等位基因2的存在以及IL -1β基因（+3953位置）的等位基因2的缺失相关。来自等位基因2（-511位置）携带者和等位基因2（+3953位置）非携带者的单核细胞在体外产生IL -1β的能力略有升高，但无统计学意义。然而，无论这些等位基因是否存在，IL -1RA等位基因2都会强烈增加IL -1β的体外产生。综上所述，这些数据表明IL -1β基因中已知的等位基因不是体外IL -1β产生的主要调节因子，但IL -1RA等位基因2（或与其紧密相关的未知等位基因）具有决定性作用。
