Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
Annu Rev Pathol. 2012;7:267-82. doi: 10.1146/annurev-pathol-011811-120900. Epub 2011 Oct 17.
Cystic fibrosis (CF), a lethal genetic disease, is characterized by substantial clinical heterogeneity. Work over the past decade has established that much of the variation is genetically conferred, and recent studies have begun to identify chromosomal locations that identify specific genes as contributing to this variation. Transcriptomic and proteomic data, sampling hundreds and thousands of genes and their products, point to pathways that are altered in the cells and tissues of CF patients. Genetic studies have examined more than half a million polymorphic sites and have identified regions, and probably genes, that contribute to the clinical heterogeneity. The combination of these approaches has great potential because genetic profiling identifies putative disease-modifying processes, and transcript and protein profiling is shedding light on the biology involved. Such studies are providing new insights into the disease, such as altered apoptotic responses, oxidative stress dysregulation, and neuronal involvement, all of which may open new therapeutic avenues to exploration.
囊性纤维化（CF）是一种致命的遗传疾病，其临床表型异质性很大。过去十年的研究已经证实，大部分变异是由遗传因素导致的，最近的研究已经开始确定染色体位置，这些位置确定了特定基因对这种变异的贡献。转录组学和蛋白质组学数据，对数百个甚至数千个基因及其产物进行采样，指出了 CF 患者细胞和组织中发生改变的途径。遗传研究已经检查了超过 50 万个多态性位点，并确定了可能导致临床异质性的区域和基因。这些方法的结合具有巨大的潜力，因为遗传分析可以确定潜在的疾病修饰过程，而转录组和蛋白质组学分析则揭示了所涉及的生物学过程。这些研究为疾病提供了新的见解，例如改变的细胞凋亡反应、氧化应激失调和神经元参与，所有这些都可能开辟新的治疗途径。
