The genetics of lupus: a functional perspective.
The genetics of lupus: a functional perspective.
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狼疮的遗传学：功能视角。
DOI：
10.1186/ar3844
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发表时间：
2012-05-29
影响因子：
4.9
通讯作者：
Cunninghame Graham DS
中科院分区：
文献类型：
--
作者：
Guerra SG;Vyse TJ;Cunninghame Graham DS
系统性红斑狼疮(SLE)是一种具有很强遗传成分的自身免疫性疾病，以慢性炎症和抗核自身抗体的产生为特征。在全基因组关联研究(GWASs)时代，阐明SLE中存在的遗传因素一直是一项非常成功的努力；已经绘制了28个已证实的疾病易感基因座。在这篇综述中，我们总结了目前对狼疮遗传学的理解，并将重点放在迄今发现的最强相关风险基因座(P<；1.0×10−8)上。虽然这些基因座只占遗传遗传力的不到10%，因此不能解释疾病的大部分遗传性，但它们确实暗示了重要的途径，有助于SLE的发病。因此，综述的主要焦点是概述已知相关基因座中的遗传变异，然后探索相关变异的潜在功能后果。我们还强调了这些基因座与其他自身免疫性疾病的遗传重叠，这表明了共同的致病机制。我们将讨论开发功能分析的重要性，每一种功能分析都将有助于我们进一步了解这些相关的变异和基因座。最后，我们指出，进行更大规模的系统性红斑狼疮GWAS，并应用一套更有针对性的方法，如免疫芯片和下一代测序方法，对于识别更多的基因座和增强我们对SLE发病机制的理解是重要的。
Systemic lupus erythematosus (SLE) is an autoimmune disease with a strong genetic component and is characterized by chronic inflammation and the production of anti-nuclear auto-antibodies. In the era of genome-wide association studies (GWASs), elucidating the genetic factors present in SLE has been a very successful endeavor; 28 confirmed disease susceptibility loci have been mapped. In this review, we summarize the current understanding of the genetics of lupus and focus on the strongest associated risk loci found to date (P <1.0 × 10−8). Although these loci account for less than 10% of the genetic heritability and therefore do not account for the bulk of the disease heritability, they do implicate important pathways, which contribute to SLE pathogenesis. Consequently, the main focus of the review is to outline the genetic variants in the known associated loci and then to explore the potential functional consequences of the associated variants. We also highlight the genetic overlap of these loci with other autoimmune diseases, which indicates common pathogenic mechanisms. The importance of developing functional assays will be discussed and each of them will be instrumental in furthering our understanding of these associated variants and loci. Finally, we indicate that performing a larger SLE GWAS and applying a more targeted set of methods, such as the ImmunoChip and next generation sequencing methodology, are important for identifying additional loci and enhancing our understanding of the pathogenesis of SLE.
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影响因子：
30.8
作者：
通讯作者：
--
DOI：
10.1038/nrrheum.2010.176
发表时间：
2010-12
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
通讯作者：
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影响因子：
30.5
作者：
Farrar, JD;Smith, JD;Murphy, KM
通讯作者：
Murphy, KM
影响因子：
13.2
作者：
BANNISTER, KM;HAY, J;WOODROFFE, AJ
通讯作者：
WOODROFFE, AJ
影响因子：
5.4
作者：
Eyquem, S;Chemin, K;Bories, JC
通讯作者：
Bories, JC