Update on gene modifiers in cystic fibrosis.
Update on gene modifiers in cystic fibrosis.
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DOI：
10.1097/mcp.0b013e3283121cdc
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发表时间：
2008-11
影响因子：
3.3
通讯作者：
Cutting GR
中科院分区：
文献类型：
--
作者：
Collaco JM;Cutting GR
囊性纤维化是一种常见的、限制生命的单基因疾病，其典型表现为进行性支气管扩张、胰腺外分泌功能障碍和反复的鼻窦肺部感染。虽然导致CFTR的基因在1989年就已被描述，但越来越明显的是，修饰基因和环境因素在决定疾病，特别是肺部疾病的严重程度中起着重要的作用。确定这些因素对于设计治疗和其他干预措施以降低与这种疾病相关的发病率和死亡率至关重要。虽然许多基因被认为是CF的潜在修饰基因，但只有少数基因经受住了复制的考验。一些重复的发现表明，影响炎症和感染反应的基因在改变CF肺部疾病严重程度方面发挥着关键作用。CFTR型、修饰基因和环境因素之间的相互作用已被证明影响CF患者的肺功能测量和感染状态。已证实有几个基因影响慢性萎缩性胃炎的病情严重程度。此外，基因-基因和基因-环境相互作用很可能解释了肺部疾病变异的很大一部分原因。正在进行的全基因组研究可能会发现新的遗传修饰物。继续探索CF的遗传和非遗传修饰物的作用，可能会产生对抗这种衰弱疾病的新选择。
Cystic fibrosis (CF) is a common, life-limiting monogenic disease, which typically manifests as progressive bronchiectasis, exocrine pancreatic dysfunction, and recurrent sinopulmonary infections. Although the gene responsible for CF (CFTR) was described in 1989, it has become increasingly evident that modifier genes and environmental factors play substantial roles in determining the severity of disease, particularly lung disease. Identifying these factors is crucial in devising therapies and other interventions to decrease the morbidity and mortality associated with this disorder. Although many genes have been proposed as potential modifiers of CF, only a handful have withstood the test of replication. Several of the replicated findings reveal that genes affecting inflammation and infection response play a key role in modifying CF lung disease severity. Interactions between CFTR genotype, modifier genes, and environmental factors have been documented to influence lung function measures and infection status in CF patients. Several genes have been demonstrated to affect disease severity in CF. Furthermore, it is likely that gene–gene and gene–environment interactions can explain a substantial portion of the variation of lung disease. Ongoing genome-wide studies are likely to identify novel genetic modifiers. Continued exploration of the role of genetic and nongenetic modifiers of CF is likely to yield new options for combating this debilitating disease.