| 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 Opportunities: | 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 Opportunities: | Scholarships in Brazil - Post-Doctoral |