Nose Masato
Department of Pathogenomics, Ehime University Graduate School of Medicine, and Proteo-Medicine Research Center, Ehime University.
Nihon Rinsho Meneki Gakkai Kaishi. 2010;33(2):43-7. doi: 10.2177/jsci.33.43.
The pathological findings in collagen disease, which was originally proposed by Klemperer et al. in 1942, show complex lesions with glomerulonephritis, vasculitis, polyarthritis and/or sialoadenitis etc. It is still controversial whether such diversity and similarity of the lesions among collagen diseases depend on an ambiguity in diagnosis or an intrinsic quality of the diseases. In the study of susceptibility loci to collagen disease in MRL mouse models, we learned that several lesions such as glomerulonephritis, vasculitis, arthritis and sialoadenitis developed in a cumulative effect of multiple gene loci, each of which by itself did not have a significant effect to induce the related phenotype, thus indicating a polygenic system. The mice developed each lesion in an additive manner with a hierarchical effect. Some of the susceptibility loci seemed to be common to those in other collagen diseases as well. Some of the positional candidate genes showed an allelic polymorphism in the coding region, possibly causing a qualitative difference in their function. As a result, a particular combination of polygenes with such an allelic polymorphism may thus play a critical role in leading the cascade reaction to develop lesions, and also a regular variation of collagen disease. This is designated as the polygene network in collagen disease.
胶原病的病理表现最初由克莱姆佩雷尔等人于1942年提出，显示出伴有肾小球肾炎、血管炎、多关节炎和/或涎腺炎等的复杂病变。胶原病之间病变的这种多样性和相似性是取决于诊断的模糊性还是疾病的内在特性，目前仍存在争议。在对MRL小鼠模型中胶原病易感基因座的研究中，我们了解到肾小球肾炎、血管炎、关节炎和涎腺炎等几种病变是由多个基因座的累积效应发展而来的，每个基因座本身对诱导相关表型并没有显著影响，因此表明这是一个多基因系统。小鼠以累加的方式并具有层级效应地发展出每种病变。一些易感基因座似乎在其他胶原病中也存在。一些定位候选基因在编码区显示出等位基因多态性，可能导致其功能上的质的差异。因此，具有这种等位基因多态性的多基因的特定组合可能在引发级联反应以发展病变以及胶原病的规律变化中起关键作用。这被称为胶原病中的多基因网络。
