Division of Rheumatology & Immunology, Medical University of South Carolina, 96 Jonathan Lucas Street, Clinical Science Building Suite 936C, Charleston, SC, 29425, USA.
Curr Rheumatol Rep. 2017 Oct 5;19(11):68. doi: 10.1007/s11926-017-0695-z.
Our understanding on genetic basis of SLE has been advanced through genome-wide association studies. We review recent progress in lupus genetics with a focus on SLE-associated loci that have been functionally characterized, and discuss the potential for clinical translation of genetics data.
Over 100 loci have been confirmed to show robust association with SLE and many share with other immune-mediated diseases. Although causative variants captured at these established loci are limited, they guide biological studies of gene targets for functional characterization which highlight the importance of aberrant recognition of self-nucleic acid, type I interferon overproduction, and defective immune cell signaling underlying the pathogenesis of SLE. Increasing examples illustrate a predictive value of genetic findings in susceptibility/prognosis prediction, clinical classification, and pharmacological implication. Genetic findings provide a foundation for better understanding of disease pathogenic mechanisms and opportunities for target selection in lupus drug development.
全基因组关联研究提高了我们对 SLE 遗传基础的认识。本文重点关注已被功能特征分析的 SLE 相关基因座，综述狼疮遗传学的最新进展，并讨论遗传数据向临床转化的潜力。
100 多个位点已被证实与 SLE 具有显著相关性，其中许多与其他免疫介导的疾病共享。尽管在这些已确定的基因座中捕获的致病变异有限，但它们指导了对基因靶点的功能特征的生物学研究，突出了自身核酸的异常识别、I 型干扰素的过度产生以及免疫细胞信号传导缺陷在 SLE 发病机制中的重要性。越来越多的例子表明遗传发现对易感性/预后预测、临床分类和药物治疗具有预测价值。遗传发现为更好地理解疾病发病机制以及在狼疮药物开发中选择靶点提供了基础。
