The GCC repeat length in the 5′UTR of MRP1 gene is polymorphic: A functional characterization of its relevance for cystic fibrosis

Elena Nicolis, Matteo Pasetto, Cristina Cigana, Ugo Pradal, Baroukh M. Assael, Paola Melotti

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Among the members of the ATP binding cassette transporter superfamily, MRPs share the closest homology with the CFTR protein, which is defective in CF disease. MRP1 has been proposed as a potential modifier gene and/or as novel target for pharmacotherapy of CF to explain the clinical benefits observed in some CF patients treated with the macrolide AZM. The 5′UTR of the MRP 1 gene contains a GCC triplet repeat that could represent a polymorphic site and affect the activity of the promoter. Methods: The MRP1 5′ flanking region was amplified by PCR from 36 CF patients and 100 non-CF subjects and the number of GCC triplets of each allele was determined by sequence and electrophoretic analysis. We performed gene reporter studies in CF airway epithelial cells 16HBE14o-AS3, in basal conditions and in the presence of AZM. Results: We found that the GCC repeat is polymorphic, ranging from 7 to 14 triplets either in CF or in non-CF subjects. Our data are preliminary and have to be confirmed on a larger population of CF subjects. The transcriptional activity of the proximal MRP1 5′ regulatory region revealed no statistically significant correlations between the number of repeats and treatment with AZM. Conclusion: We identified a novel polymorphism in the 5′UTR of MRP 1 gene that provides multiple alleles in a gene relevant for multidrug resistance as well as for CF, determining that this region is transcriptionally active and that this activity does not appear to be influenced by AZM treatment.

Original languageEnglish
JournalBMC Medical Genetics
Volume7
DOIs
Publication statusPublished - Feb 7 2006

ASJC Scopus subject areas

  • Medicine(all)
  • Genetics(clinical)

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