Department of Pathology, Tennis Court Road and CIMR, Addenbrookes Site, University of Cambridge, United Kingdom.
Immunol Lett. 2011 Jun 30;137(1-2):1-8. doi: 10.1016/j.imlet.2011.01.002. Epub 2011 Jan 22.
Given large sample sizes, whole genome screens are now able to identify even quite modest contributions of common human genetic variation to disease. These approaches, made possible by the development of high-throughput, dense SNP genotyping, find few associations stronger than those for the human MHC, in multigenic autoimmune conditions. They confirm earlier findings that the major variants affecting susceptibility and resistance to autoimmunity relate to MHC class I and class II genes. It is generally assumed, although there are few good examples, that selection for resistance to infection drives evolution of MHC variation. Many MHC-associated diseases may be the price paid for an effective immune response. Interestingly, the MHC appears to influence susceptibility to conditions unrelated to immunity, including some neuropathologies. The infectious history of the individual, conditioned by their MHC, may exert an indirect effect on these diseases, although there are hints of more direct involvement of MHC molecules in neuronal systems. Here I survey the variety of conditions associated with the MHC in relation to ideas that selection through disease resistance is dependent upon MHC variation, not only at the level of the individual, but also at the level of the population.
在样本量足够大的情况下，全基因组筛查现在能够识别出常见的人类遗传变异对疾病的影响，即使这种影响很小。这些方法是通过高通量、高密度 SNP 基因分型的发展实现的，在多基因自身免疫性疾病中，很少有比人类 MHC 更强的关联。这些方法证实了早期的发现，即影响自身免疫易感性和抵抗力的主要变异与 MHC Ⅰ类和Ⅱ类基因有关。人们普遍认为，尽管很少有很好的例子，但对感染的抵抗力的选择推动了 MHC 变异的进化。许多与 MHC 相关的疾病可能是为有效免疫反应付出的代价。有趣的是，MHC 似乎也会影响与免疫无关的疾病的易感性，包括一些神经病理学疾病。个体的感染史受 MHC 影响，可能会对这些疾病产生间接影响，尽管有迹象表明 MHC 分子更直接地参与了神经元系统。在这里，我调查了与 MHC 相关的各种疾病，并探讨了通过疾病抗性选择是否依赖于 MHC 变异的观点，不仅在个体水平上，而且在群体水平上也是如此。
