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(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

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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
[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

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