Relationship between airway ion transport and a mild pulmonary disease mutation in CFTR.
Relationship between airway ion transport and a mild pulmonary disease mutation in CFTR.
复制标题
气道离子转运与 CFTR 中轻度肺部疾病突变的关系。
DOI：
10.1164/ajrccm.155.5.9154877
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Sorscher,EJ
中科院分区：
文献类型：
--
作者：
Walker,LC;Venglarik,CJ;Aubin,G;Weatherly,MR;McCarty,NA;Lesnick,B;Ruiz,F;Clancy,JP;Sorscher,EJ
囊性纤维化（CF）患者表现出气道离子转运缺陷，但气道转运表型对改善预后的影响尚不清楚。我们研究了5例与轻度肺部疾病相关的罕见A455E突变CF患者的气道生物电特性。我们还评估了5例具有过早截断突变（G542X和R553X）的患者，其与轻度肺部疾病的关联尚未得到很好的证实。我们在体内没有发现CF跨膜调节基因（CFTR）轻度肺部疾病突变导致纠正或部分纠正的证据：(1)未受刺激的Cl-分泌；(2) β激动剂激活的Cl-分泌；(3)基础钠重吸收；或(4)阿米洛利敏感的气道钠转运。CF的早期治疗试验，包括人类基因转移试验，在很大程度上依赖于气道电位差异的改善，以确定有希望的干预措施和改善的预后。根据我们在自然发生的肺预后改善的CF患者组（A455E）中的发现，我们可以认为，在没有任何气道生物电表型改善的情况下，显著的临床获益是可能的。此外，如果存在影响特定CFTR突变（例如A455E）严重程度的遗传修饰因子，则这些修饰因子可能与体内人体气道Cl分泌无关，因为我们在A455E患者中检测到最小的Cl分泌反应。
Patients with cystic fibrosis (CF) display defects in airway ion transport, but the influence of airway transport phenotype on improved prognosis is not known. We studied airway bioelectric properties in five CF patients with the rare A455E mutation that is associated with mild pulmonary disease. We also evaluated five patients possessing premature truncation mutations (G542X and R553X) for which an association with mild pulmonary disease has not been as well established. We found no evidence in vivo that a mild lung disease mutation in the CF transmembrane regulator gene (CFTR) led to correction or partial correction of: (1) unstimulated Cl- secretion; (2) beta-agonist-activated Cl- secretion; (3) basal sodium reabsorption; or (4) amiloride-sensitive airway sodium transport. Early phase therapeutic trials in CF, including human gene transfer trials, rely heavily on improvements in airway potential difference to identify promising interventions and an improved prognosis. Based on our findings in a naturally occurring group of CF patients with an improved pulmonary prognosis (A455E), one can argue that marked clinical benefit might be possible without any improvement whatsoever in airway bioelectric phenotype. Moreover, if genetic modifiers exist that influence the severity of a particular CFTR mutation (e.g., A455E), these may be independent of human airway Cl-secretion in vivo, since we detected minimal Cl--secretory responses in patients with A455E.