Advanced search
Start date
Betweenand
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

Full text
Author(s):
Kmit, Arthur [1, 2] ; Lima Marson, Fernando Augusto [1, 2] ; Pereira, Stephanie Villa-Nova [2] ; Vinagre, Adriana Mendes [1] ; Leite, Gabriela Silva [1] ; Servidoni, Maria Fatima [1] ; Ribeiro, Jose Dirceu [1] ; Ribeiro, Antonio Fernando [1] ; Bertuzzo, Carmen Silvia [2] ; Amaral, Margarida Duarte [3]
Total Authors: 10
Affiliation:
[1] Univ Estadual Campinas, Fac Med Sci, Dept Pediat, Campinas, SP - Brazil
[2] Univ Estadual Campinas, Fac Med Sci, Dept Med Genet & Genom Med, Tessalia Vieira de Camargo 126, BR-13083887 Campinas, SP - Brazil
[3] Univ Lisbon, Fac Sci, BioISI Biosyst & Integrat Sci Inst, Lisbon - Portugal
Total Affiliations: 3
Document type: Journal article
Source: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE; v. 1865, n. 6, p. 1323-1331, JUN 1 2019.
Web of Science Citations: 1
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. (AU)

FAPESP's process: 15/12183-8 - Identification of prevalent mutations and clinical and functional characterization of children and adults with primary ciliary dyskinesia
Grantee:Jose Dirceu Ribeiro
Support type: Regular Research Grants
FAPESP's process: 15/12858-5 - Identification of prevalent mutations and clinical and functional characterization of children and adults with primary ciliary dyskinesia
Grantee:Fernando Augusto de Lima Marson
Support type: Scholarships in Brazil - Post-Doctorate