INTRODUCTION Variability in disease severity and CFTR modulator responses exists between patients with identical CFTR genotypes. Here, we characterized transcription, translation and function of R117H-CFTR using intestinal organoids and correlated them with in vitro responses to ivacaftor (VX-770). METHODS Organoids were generated from individuals possessing at least one R117H-CFTR allele. The forskolin-induced swelling (FIS) assay was used to measure CFTR function and response to VX-770 treatment. R117H-CFTR protein and mRNA expression levels were determined in parallel and Pearson's correlation coefficients were assessed. RESULTS Variability in R117H-CFTR FIS responses was observed and correlated significantly with mRNA and protein expression. Response to VX-770 treatment in organoids correlated with mRNA and protein expression as well. CONCLUSIONS Our results indicate that gene expression, protein expression and CFTR function are strongly correlated in organoids from people with CFTR-R117H-7T/9T, which may suggest that CFTR gene expression may have consequences for CF diagnosis, prognosis and therapeutic benefit.

中文翻译：

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R117H-CFTR 功能和对 VX-770 的反应与肠道类器官中的 mRNA 和蛋白质表达相关

介绍 具有相同 CFTR 基因型的患者之间存在疾病严重程度和 CFTR 调节剂反应的差异。在这里，我们使用肠道类器官表征了 R117H-CFTR 的转录、翻译和功能，并将它们与体外对 ivacaftor (VX-770) 的反应相关联。方法 从拥有至少一个 R117H-CFTR 等位基因的个体中产生类器官。毛喉素诱导肿胀 (FIS) 测定用于测量 CFTR 功能和对 VX-770 治疗的反应。R117H-CFTR 蛋白和 mRNA 表达水平平行测定，并评估 Pearson 相关系数。结果 观察到 R117H-CFTR FIS 反应的变异性，并与 mRNA 和蛋白质表达显着相关。类器官对 VX-770 治疗的反应也与 mRNA 和蛋白质表达相关。