Immunogenetics of systemic lupus erythematosus: A comprehensive review.
Immunogenetics of systemic lupus erythematosus: A comprehensive review.
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DOI：
10.1016/j.jaut.2015.08.004
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发表时间：
2015-11
影响因子：
12.8
通讯作者：
Niewold TB
中科院分区：
文献类型：
--
作者：
Ghodke-Puranik Y;Niewold TB
近年来，我们对系统性红斑狼疮遗传基础的了解进展迅速。虽然许多遗传多态性与疾病易感性有关，但下一个主要步骤是将这些遗传多态性整合到人类疾病的分子机制和细胞免疫学中。在这篇综述中，我们总结了最近在这一领域的一些工作，包括SLE中I型IFN反应的遗传学，包括多基因和单基因因素，以及表观遗传影响。HLA和非HLA多态性对SLE复杂遗传学的贡献进行了综述。我们还回顾了最近关于导致单基因slea样综合征的特定基因缺陷的报道。本文对常见sled风险变异的分子功能进行了深入的回顾，包括启动子和增强子元件的调控变化和编码变化多态性，以及开始定义这些多态性在免疫系统中的分子和细胞功能的研究。我们讨论了表观遗传对狼疮的影响，重点是微rna的表达和结合，以及调节狼疮发病机制中各种基因表达水平的表观遗传修饰，以及表观遗传标记修饰狼疮易感基因的方式。本综述总结的工作为人类SLE的生物学和分子机制提供了一个迷人的窗口。了解人类疾病的因果遗传变异的功能机制极大地促进了我们将遗传关联转化为个性化护理的能力，并可能确定与人类SLE疾病机制相关的新治疗靶点。
Our understanding of the genetic basis of systemic lupus erythematosus has progressed rapidly in recent years. While many genetic polymorphisms have been associated with disease susceptibility, the next major step involves integrating these genetic polymorphisms into the molecular mechanisms and cellular immunology of the human disease. In this review, we summarize some recent work in this area, including the genetics of the type I IFN response in SLE, including polygenic and monogenic factors, as well as epigenetic influences. Contributions of both HLA and non-HLA polymorphisms to the complex genetics of SLE are reviewed. We also review recent reports of specific gene deficits leading to monogenic SLE-like syndromes. The molecular functions of common SLE-risk variants are reviewed in depth, including regulatory variations in promoter and enhancer elements and coding-change polymorphisms, and studies which are beginning to define the molecular and cellular functions of these polymorphisms in the immune system. We discuss epigenetic influences on lupus, with an emphasis on micro-RNA expression and binding, as well as epigenetic modifications that regulate the expression levels of various genes involved in SLE pathogenesis and the ways epigenetic marks modify SLE susceptibility genes. The work summarized in this review provides a fascinating window into the biology and molecular mechanisms of human SLE. Understanding the functional mechanisms of causal genetic variants underlying the human disease greatly facilitates our ability to translate genetic associations toward personalized care, and may identify new therapeutic targets relevant to human SLE disease mechanisms.