Morahan G, Kaur G, Singh M, Rapthap C C, Kumar N, Katoch K, Mehra N K, Huang D
Diabetes Research Centre, Western Australia Institute for Medical Research, Perth, WA, Australia.
Tissue Antigens. 2007 Apr;69 Suppl 1:234-6. doi: 10.1111/j.1399-0039.2006.773_3.x.
There is a great range in outcomes after mycobacterial infections, and this is probably due to individual variation in immune responses. One of the key cytokine regulators of the immune response is interleukin (IL-) 12. The IL12B gene encodes the p40 chain of both IL-12 and IL-23 and it has two major variant sites at which different alleles are associated with increased levels of gene expression and with susceptibility to a range of immune-related diseases. We hypothesized that IL12B variants associated with increased expression would be as associated with susceptibility to persistent mycobacterial infection. We tested this hypothesis by genotyping Indian subjects, having either leprosy or tuberculosis (TB), as well as ethnically matched controls. Subjects with leprosy were less likely to have the 3'UTR genotype associated with lower IL12B expression (P= 0.001). Subjects with TB were not only more likely to have the high-expressing IL12B promoter genotype (P= 0.01) but also more likely to have this in the same haplotype with the high expressing 3'UTR allele (P= 0.0009). These results suggest these infectious diseases may be improved by modulating IL-l2p40 production.
分枝杆菌感染后的结果差异很大，这可能是由于免疫反应的个体差异所致。免疫反应的关键细胞因子调节因子之一是白细胞介素（IL-）12。IL12B基因编码IL-12和IL-23的p40链，它有两个主要变异位点，不同的等位基因与基因表达水平的增加以及对一系列免疫相关疾病的易感性有关。我们假设与表达增加相关的IL12B变异也与持续性分枝杆菌感染的易感性有关。我们通过对患有麻风病或结核病（TB）的印度受试者以及种族匹配的对照进行基因分型来检验这一假设。患有麻风病的受试者携带与较低IL12B表达相关的3'UTR基因型的可能性较小（P = 0.001）。患有结核病的受试者不仅更有可能拥有高表达的IL12B启动子基因型（P = 0.01），而且更有可能在与高表达的3'UTR等位基因相同的单倍型中拥有该基因型（P = 0.0009）。这些结果表明，通过调节IL-12p40的产生可能会改善这些传染病。
