Extent of rescue of F508del-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.
Biochim Biophys Acta Mol Basis Dis
; 1865(6): 1323-1331, 2019 06 01.
Article
em En
| MEDLINE
| ID: mdl-30716472
ABSTRACT
BACKGROUND:
We analyzed the CFTR response to VX-809/VX-770 drugs in conditionally reprogrammed cells (CRC) of human nasal epithelium (HNE) from F508del/F508del patients based on SNP rs7512462 in the Solute Carrier Family 26, Member 9 (SLC26A9; MIM 608481) gene.METHODS:
The Isc-eq measurements of primary nasal epithelial cells from F508del/F508del patients (nâ¯=â¯12) for CFTR function were performed in micro Ussing chambers and compared with non-CF controls (nâ¯=â¯2). Data were analyzed according to the rs7512462 genotype which were determined by real-time PCR.RESULTS:
The CRC-HNE cells from F508del/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-809â¯+â¯VX-770. The rs7512462*CCâ¯+â¯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 [Cl-] and body mass index of patients also evidenced an association with the rs7512462 genotype.CONCLUSION:
The CFTR function can be performed in F508del/F508del patient-derived CRC-HNEs and its function and responses to VX-809â¯+â¯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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antiporters
/
Quinolonas
/
Regulador de Condutância Transmembrana em Fibrose Cística
/
Células Epiteliais
/
Benzodioxóis
/
Agonistas dos Canais de Cloreto
/
Transportadores de Sulfato
/
Aminofenóis
/
Aminopiridinas
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article