Recent insights into the genetic basis of systemic lupus erythematosus.
Recent insights into the genetic basis of systemic lupus erythematosus.
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对全身性红斑狼疮的遗传基础的最新见解。
DOI：
10.1038/gene.2009.39
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发表时间：
2009-07
影响因子：
5
通讯作者：
Harley, J. B.
中科院分区：
文献类型：
--
作者：
Moser, K. L.;Kelly, J. A.;Lessard, C. J.;Harley, J. B.
遗传变异在20世纪70年代首次被证明是系统性红斑狼疮（SLE或狼疮）的部分原因，与人类白细胞抗原（HLA）区域相关。近40年后，在越来越强大的遗传学方法的帮助下，现在已知超过25个基因有助于使个体易患狼疮的机制。这些基因座中有一半以上是在过去两年中发现的，这突出了最近全基因组关联方法在SLE中的非凡成功。目前已确定的遗传风险因素包括MHC区域（多个基因）、IRF 5、ITGAM、STAT 4、BLK、BANK 1、PDCD 1、PTPN 22、TNFSF 4、TNFAIP 3、SPP 1、ATG 5、XKR 6、PXK、某些Fcγ受体中的等位基因，以及几种补体成分（包括C1q、C4和C2）的缺陷。在这里回顾，这些基因中的许多属于关键途径，是与以前的研究牵连免疫复合物，宿主免疫信号转导和干扰素途径在SLE的发病机制是一致的。其他遗传位点没有已知的功能或明显的免疫学作用，并有可能揭示新的疾病机制。当然，随着我们对SLE遗传病因学的理解不断成熟，将出现重要的新机会，为这种复杂的自身免疫性疾病开发更有针对性和更有效的诊断和临床管理工具。
Genetic variation was first shown to be part of the cause of systemic lupus erythematosus (SLE or lupus) in the 1970s with associations in the human leukocyte antigen (HLA) region. Almost four decades later, and with the help of increasingly powerful genetic approaches, more than 25 genes are now known to contribute to the mechanisms that predispose individuals to lupus. Over half of these loci have been discovered in the past two years, underscoring the extraordinary success of recent genome-wide association approaches in SLE. The now well established genetic risk factors include alleles in the MHC region (multiple genes), IRF5, ITGAM, STAT4, BLK, BANK1, PDCD1, PTPN22, TNFSF4, TNFAIP3, SPP1, ATG5, XKR6, PXK, some of the Fcγ receptors, and deficiencies in several complement components, including C1q, C4, and C2. As reviewed here, many of these genes fall into key pathways that are consistent with previous studies implicating immune complexes, host immune signal transduction, and interferon pathways in the pathogenesis of SLE. Other genetic loci have no known function or apparent immunological role and have the potential to reveal novel disease mechanisms. Certainly, as our understanding of the genetic etiology of SLE continues to mature, important new opportunities will emerge for developing more targeted and effective diagnostic and clinical management tools for this complex autoimmune disease.
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影响因子：
30.8
作者：
通讯作者：
--
DOI：
10.4049/jimmunol.182.1.34
发表时间：
2009-01-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kariuki SN;Kirou KA;MacDermott EJ;Barillas-Arias L;Crow MK;Niewold TB
通讯作者：
Niewold TB
影响因子：
--
作者：
Edberg, JC;Langefeld, CD;Kimberly, RP
通讯作者：
Kimberly, RP
6q23 上 TNFAIP3 附近的遗传变异与系统性红斑狼疮相关。
影响因子：
30.8
作者：
Graham, Robert R.;Cotsapas, Chris;Davies, Leela;Hackett, Rachel;Lessard, Christopher J.;Leon, Joanlise M.;Burtt, Noel P.;Guiducci, Candace;Parkin, Melissa;Gates, Casey;Plenge, Robert M.;Behrens, Timothy W.;Wither, Joan E.;Rioux, John D.;Fortin, Paul R.;Graham, Deborah Cunninghame;Wong, Andrew K.;Vyse, Timothy J.;Daly, Mark J.;Altshuler, David;Moser, Kathy L.;Gaffney, Patrick M.
通讯作者：
Gaffney, Patrick M.
影响因子：
9.8
作者：
Gorlov, Ivan P.;Gorlova, Olga Y.;Amos, Christopher I.
通讯作者：
Amos, Christopher I.