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Type: Artigo
Title: Extent of rescue of F508de1-CFTR function by VX-809 and VX-770 in human nasal epithelial cells correlates with SNP rs7512462 in SLC26A9 gene in F508del/F508del cystic fibrosis patients
Author: Kmit, Arthur
Lima Marson, Fernando Augusto
Pereira, Stephanie Villa-Nova
Vinagre, Adriana Mendes
Leite, Gabriela Silva
Servidoni, Maria Fatima
Ribeiro, Jose Dirceu
Ribeiro, Antonio Fernando
Bertuzzo, Carmen Silvia
Amaral, Margarida Duarte
Abstract: Background: We analyzed the CFTR response to VX-809/VX-770 drugs in conditionally reprogrammed cells (CRC) of human nasal epithelium (HNE) from F508de1/F508del patients based on SNP rs7512462 in the Solute Carrier Family 26, Member 9 (SLC26A9; MIM: 608481) gene. Methods: The measurements of primary nasal epithelial cells from F508del/F508de1 patients (n = 12) for CFTR function were performed in micro Ussing chambers and compared with non-CF controls (n = 2). Data were analyzed according to the rs7512462 genotype which were determined by real-time PCR. Results: The CRC-HNE cells from F508de1/F508del patients evidenced high variability in the basal levels of CFTR function. Also, the rs7512462*C allele showed an increased basal CFTR function and higher responses to VX-809 + VX-770. The rs7512462*CC + CT genotypes together evidenced CFTR function levels of 14.89% relatively to wt/wt (rs7512462*CT alone-15.29%) i.e., almost double of rs7512462*TT (7.13%). Furthermore, sweat Cr and body mass index of patients also evidenced an association with the rs7512462 genotype. Conclusion: The CFTR function can be performed in F508de1/F508del patient-derived CRC-HNEs and its function and responses to VX-809 + VX-770 combination as well as clinical data, are all associated with the rs7512462 variant, which partially sheds light on the generally inter-individual phenotypic variability and in personalized responses to CFTR modulator drugs
Subject: Células epiteliais
Fibrose cística
Country: Países Baixos
Editor: Elsevier
Rights: Fechado
Identifier DOI: 10.1016/j.bbadis.2019.01.029
Date Issue: 2019
Appears in Collections:FCM - Artigos e Outros Documentos

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