Gazouli Maria, Koundourakis Aimilios, Ikonomopoulos John, Gialafos Elias J, Rapti Aggeliki, Gorgoulis Vassilis G, Kittas Christos
Department of Histology-Embryology, School of Medicine, University of Athens, Athens, Greece.
Sarcoidosis Vasc Diffuse Lung Dis. 2006 Mar;23(1):23-9.
Sarcoidosis, similarly to Crohn's disease (CD), is a complex inflammatory disease of unknown etiology. The belief that a genetic susceptibility to the development of sarcoidosis exists was derived from observations of familial clustering of sarcoidosis cases and racial differences in disease prevalence. Taking into account the remarkable similarity in the immunopathophysiology of sarcoidosis and CD, and in further exploring the genetic background of sarcoidosis, we study gene polymorphisms known for their implication in CD. These polymorphisms are in the CARD15/NOD2 gene (R702W, G908R and 3020insC), as well as mutations in the promoter of the CD14 gene (T/C at position -159) and in the TLR4 gene (Asp299Gly and Thr399Ile).
DNA was obtained from 100 sarcoidosis patients and 150 healthy individuals. Genotyping was performed by allele specific PCR or by PCR-RFLP analysis.
Although CARD 15/NOD2 mutations were more frequent in cases than in controls, the difference was significant only for the G908R polymorphism (p = 0.024). Interestingly, the same was recorded with reference to the T allele (p = 0.002) and TT genotype (p = 0.017) frequencies of the CD14 promoter. No differences were observed in the 299Gly and 399Ile allele frequencies between patients and controls. Finally, the co-existence of a mutation in the CARD15/NOD2 and the CD14 genes was associated with sarcoidosis at a higher level of significance than any of these mutations separately.
Our results suggest that the G908R mutation of the CARD15/NOD2 gene, as well as the T allele and TT genotype of the CD14 promoter are associated with increased susceptibility for developing sarcoidosis.
结节病与克罗恩病（CD）类似，是一种病因不明的复杂炎症性疾病。结节病存在遗传易感性这一观点源于对结节病病例家族聚集性以及疾病患病率种族差异的观察。考虑到结节病和CD在免疫病理生理学方面的显著相似性，并进一步探索结节病的遗传背景，我们研究了已知与CD相关的基因多态性。这些多态性存在于CARD15/NOD2基因（R702W、G908R和3020insC），以及CD14基因启动子（-159位的T/C）和TLR4基因（Asp299Gly和Thr399Ile）的突变中。
从100例结节病患者和150名健康个体中获取DNA。通过等位基因特异性PCR或PCR-RFLP分析进行基因分型。
虽然CARD 15/NOD2突变在病例中比在对照中更常见，但差异仅在G908R多态性方面具有统计学意义（p = 0.024）。有趣的是，CD14启动子的T等位基因（p = 0.002）和TT基因型（p = 0.017）频率也有同样的情况。患者和对照之间在299Gly和399Ile等位基因频率上未观察到差异。最后，CARD15/NOD2和CD14基因中的突变共同存在与结节病的关联程度比任何一个单独的突变都更高，具有更高的统计学意义。
我们的结果表明，CARD15/NOD2基因的G908R突变以及CD14启动子的T等位基因和TT基因型与患结节病的易感性增加有关。
