Evaluation of MRP1-5 Gene Expression in Cystic Fibrosis Patients Homozygous for the [DELTA]F508 Mutation.
HURBAIN, ILSE; SERMET-GAUDELUS, ISABELLE; VALLEE, BENOIT; FEUILLET, MARIE-NOELLE; LENOIR, GERARD; BERNAUDIN, JEAN-FRANCOIS; EDELMAN, AND, ALEKSANDER; FAJAC, ANNE
54(5):627-634, November 2003.
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Cystic fibrosis (CF), due to mutations of the cystic fibrosis transmembrane conductance regulator (CFTR), exhibits a wide range of disease severity, even among [DELTA]F508 homozygous patients, and the mechanisms of this variability have yet to be elucidated. In view of the close structural homology and possible functional overlap between CFTR and Multidrug Resistance-associated Proteins (MRPs), MRPs were investigated as potentially relevant factors in CF pathophysiology. MRP1-5 gene expression was analyzed in nasal respiratory epithelial cells from [DELTA]F508 homozygous patients (n = 19) and control subjects (n = 20) using semiquantitative RT-PCR. Significantly lower MRP1 and MRP5 transcript levels were found in CF patients than in control subjects. MRP1 and MRP5 transcript levels were strongly correlated (r = 0.71). In CF patients, low MRP1 transcript levels were associated with more severe disease as assessed by the Shwachman score. A relation was also observed between MRP1 levels and presence of a cAMP-independent chloride conductive pathway, as determined by a halide-sensitive fluorescent assay. These results suggest that MRPs, especially MRP1, might play a role in CF phenotype and might therefore constitute a target for a novel pharmacotherapy of CF.
(C) International Pediatrics Research Foundation, Inc. 2003. All Rights Reserved.