Ahmed S Sohail, Tan Filemon K
Department of Internal Medicine, University of Texas Medical School-Houston, Texas 77030, USA.
Curr Opin Rheumatol. 2003 Nov;15(6):766-71. doi: 10.1097/00002281-200311000-00014.
Systemic sclerosis, or scleroderma, is an uncommon autoimmune connective tissue disease that results in systemic fibrosis. Its etiologic basis remains unclear. The pathogenesis of systemic sclerosis involves a proliferative and obliterative vasculopathy resulting from endothelial cell dysfunction, extensive fibrosis secondary to fibroblast activation, and autoimmunity as demonstrated by the presence of disease-specific autoantibodies. Although there is no clear and convincing evidence for an environmental trigger in most cases, accumulating data emphasize the role of genetic factors in systemic sclerosis. As in other complex human diseases, multiple genes likely contribute to disease susceptibility and the clinical manifestations of systemic sclerosis. This review will cover the application of genomics to the complex genetics of systemic sclerosis.
The following review is an update on novel targets identified in scleroderma based on published reports (May 2000-May 2003) of mutation/polymorphism analysis (using SNP and haplotyping), the results from a recent genome-wide scan on a Native American population with systemic sclerosis, and gene expression studies (microarrays).
The use of genomics has revealed novel targets and genetic associations that may contribute to the cause, the onset, and the subsequent pathologic changes that constitute systemic sclerosis. The identification of potential candidates for gene therapy or disease-specific targets amenable to pharmacologic intervention will benefit patients with systemic sclerosis who are currently being treated for their symptoms and not the disease process itself.
系统性硬化症，又称硬皮病，是一种罕见的自身免疫性结缔组织疾病，可导致全身纤维化。其病因尚不清楚。系统性硬化症的发病机制涉及内皮细胞功能障碍导致的增殖性和闭塞性血管病变、成纤维细胞活化继发的广泛纤维化以及疾病特异性自身抗体的存在所证明的自身免疫。尽管在大多数情况下没有明确且令人信服的证据表明存在环境触发因素，但越来越多的数据强调了遗传因素在系统性硬化症中的作用。与其他复杂的人类疾病一样，多个基因可能导致系统性硬化症的易感性和临床表现。本综述将涵盖基因组学在系统性硬化症复杂遗传学中的应用。
以下综述是基于已发表的报告（2000年5月至2003年5月）对硬皮病中确定的新靶点的更新，这些报告涉及突变/多态性分析（使用单核苷酸多态性和单倍型分型）、最近对一个患有系统性硬化症的美洲原住民群体进行的全基因组扫描结果以及基因表达研究（微阵列）。
基因组学的应用揭示了可能导致系统性硬化症病因、发病及后续病理变化的新靶点和遗传关联。确定基因治疗的潜在候选者或适合药物干预的疾病特异性靶点，将使目前仅针对症状而非疾病进程进行治疗的系统性硬化症患者受益。
