The genetics of scleroderma: looking into the postgenomic era.
The genetics of scleroderma: looking into the postgenomic era.
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DOI：
10.1097/bor.0b013e328358575b
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发表时间：
2012-11
影响因子：
5.1
通讯作者：
Mayes MD
中科院分区：
文献类型：
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作者：
Mayes MD
过去十年，在了解系统性硬化症的遗传关联以解释观察到的遗传性方面取得了巨大进展。本次审查重点介绍了最新的发现，并将其置于拟议的职能角色的背景下。目前已鉴定出 30 多个基因和基因区域为硬皮病易感位点。其中包括人类白细胞抗原 (HLA) 和非 HLA 基因，其中大多数涉及免疫相关途径和免疫功能调节剂。许多这些关联在其他系统性自身免疫性疾病中也有报道，表明有多种自身免疫基因导致疾病的发生。尽管取得了这些进展，但仅解释了系统性硬化症遗传性的一小部分。正在进行的研究包括精细绘图和测序研究，以识别因果变异，而其他研究则侧重于这些变异的功能后果，以便确定这些遗传变异与疾病易感性之间的联系。这些知识应该有助于对这种疾病进行更有针对性和更有效的治疗。
The last decade has seen enormous progress in understanding genetic associations of systemic sclerosis to explain the observed heritability. This review highlights the most recent findings and places them in the context of proposed functional roles. Over 30 genes and gene regions have now been identified as scleroderma susceptibility loci. These include both human leukocyte antigen (HLA) and non-HLA genes, most of which involve immune-related pathways and modifiers of immune function. Many of these associations have also been reported in other systemic autoimmune diseases and suggest that there are multiple autoimmunity genes resulting in disease occurrence. In spite of these advances, only a small proportion of the heritability of systemic sclerosis has been explained. Ongoing studies include fine mapping and sequencing studies to identify causal variants, whereas other studies focus on functional consequences of these variants in order to identify the link between these genetic variants and disease susceptibility. Such knowledge should lead to more targeted and effective treatment in this disease.