The genetic approach in pulmonary fibrosis: can it provide clues to this complex disease?
The genetic approach in pulmonary fibrosis: can it provide clues to this complex disease?
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DOI：
10.1513/pats.200512-137tk
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发表时间：
2006-06-01
期刊：
影响因子：
--
通讯作者：
Loyd, James E
中科院分区：
文献类型：
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作者：
Lawson, William E;Loyd, James E
多名研究人员对特发性肺纤维化人群进行了遗传研究，试图确定疾病的遗传联系，希望这将提高对疾病发病机制和治疗靶点途径的理解。使用候选基因方法对多个基因进行了评估，但取得了有限的成功，结果表明存在疾病修饰作用而不是致病作用。使用这种方法，已经观察到特发性肺纤维化与编码白介素-1受体拮抗剂、肿瘤坏死因子- α和补体受体1基因的特异性多态性之间的关联。最近研究人员使用家族性肺纤维化队列来评估与特发性肺纤维化相关的基因突变。利用一个肺纤维化家族，编码表面活性剂蛋白C的基因突变被确定为该家族肺纤维化的原因。随后，另一个特发性肺纤维化患者被鉴定为表面活性剂蛋白C的不同突变，尽管在特发性肺纤维化患者中很少发现，但这些表面活性剂蛋白C突变突出了肺泡上皮在疾病发病机制中的重要性。最近，三个主要研究中心的研究人员进行了一项合作，收集了迄今为止最大的肺纤维化家族，希望这项工作能够识别与特发性肺纤维化相关的基因突变。如果在这项研究中确定了与特发性肺纤维化的遗传联系，那么研究人员就可以针对这些基因和基因产物所涉及的途径，帮助确定这种疾病的潜在治疗方案。
Multiple investigators have undertaken genetic studies in idiopathic pulmonary fibrosis populations in attempts to define genetic links to disease in hopes that this would improve understanding of disease pathogenesis and target pathways for therapy. Multiple genes have been evaluated using a candidate gene approach with limited success, with results suggesting a disease modifier effect rather than a disease causing effect. Using this approach, associations have been observed between idiopathic pulmonary fibrosis and specific polymorphisms in genes encoding interleukin-1 receptor antagonist, tumor necrosis factor-alpha, and complement receptor 1. Recently investigators have used familial pulmonary fibrosis cohorts to evaluate for genetic mutations associated with idiopathic pulmonary fibrosis. Using one pulmonary fibrosis kindred, a mutation in the gene encoding surfactant protein C was identified as the cause of pulmonary fibrosis in this family. Subsequently, another individual with idiopathic pulmonary fibrosis was identified with a different mutation in surfactant protein C. Though rarely found in patients with idiopathic pulmonary fibrosis, these surfactant protein C mutations highlight the importance of the alveolar epithelium in disease pathogenesis. A recent collaboration between investigators at three major centers has resulted in the largest collection of families with pulmonary fibrosis to date, with hopes that this effort will identify genetic mutations associated with idiopathic pulmonary fibrosis. If genetic links to idiopathic pulmonary fibrosis are defined in this study, then the pathways involved with these genes and gene products can be targeted by investigators to help identify potential treatment options for this disease.