Hill Natasha J, King Cecile, Flodstrom-Tullberg Malin
Centre for Diabetes and Metabolic Medicine, Institute of Cell and Molecular Sciences, Barts and the London School of Medicine and Dentistry, 4 Newark Street London E1 2AT, UK.
Front Biosci. 2008 May 1;13:4838-51. doi: 10.2741/3043.
In this review we will discuss recent progress from studies on the genetic basis of autoimmune disease and how this has advanced our understanding of the processes behind disease susceptibility and pathogenesis. We review the genetic associations with autoimmune and inflammatory disease discovered in the latest genome-wide association (GWA) scans, and discuss the importance of animal models both for generating candidates and for mechanistic studies. Investigating the natural variants of key immune regulatory molecules can give us an additional level of insight into their function and physiological regulation over gene knockouts. New data showing the association of multiple genes involved in pathogen defense highlights the potential role of infection in autoimmunity, and a more complete understanding of the pathways defective in genetically susceptible individuals will also give us a handle on how environmental and epigenetic factors may be impacting disease.
在本综述中，我们将讨论自身免疫性疾病遗传基础研究的最新进展，以及这如何深化了我们对疾病易感性和发病机制背后过程的理解。我们回顾了在最新的全基因组关联（GWA）扫描中发现的与自身免疫性和炎性疾病的遗传关联，并讨论了动物模型对于生成候选基因和进行机制研究的重要性。研究关键免疫调节分子的自然变异可以让我们对其功能以及基因敲除后的生理调节有更深入的了解。新数据显示参与病原体防御的多个基因之间存在关联，这凸显了感染在自身免疫中的潜在作用，而更全面地了解基因易感性个体中存在缺陷的通路，也将有助于我们掌握环境和表观遗传因素可能如何影响疾病。
