title: The GCC repeat length in the 5'UTR of MRP1 gene is polymorphic: a functional characterization of its relevance for cystic fibrosis.
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 MRP1 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.
  
  
  CONCLUSIONS
  We identified a novel polymorphism in the 5'UTR of MRP1 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.
authors.affiliation: Cystic Fibrosis Center, Azienda Ospedaliera di Verona, Piazzale Stefani 1, 37126 Verona, Italy. elenni@libero.it
authors.forename: Elena
authors.initials: E
authors.lastname: Nicolis
authors.forename: Matteo
authors.initials: M
authors.lastname: Pasetto
authors.forename: Cristina
authors.initials: C
authors.lastname: Cigana
authors.forename: Ugo
authors.initials: U
authors.lastname: Pradal
authors.forename: Baroukh M
authors.initials: BM
authors.lastname: Assael
authors.forename: Paola
authors.initials: P
authors.lastname: Melotti
mesh_terms: D024506:5' Flanking Region; D020121:5' Untranslated Regions / Q000737:chemistry / Q000235:genetics*; D002460:Cell Line; D003550:Cystic Fibrosis / Q000235:genetics*; D005787:Gene Frequency; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis / Q000235:genetics*; D011110:Polymorphism, Genetic; D014158:Transcription, Genetic; D018911:Trinucleotide Repeats
chemical_list: D020121:5' Untranslated Regions; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C421109:multidrug resistance-associated protein 1