title: Genetic variation of the ABC transporter gene ABCC1 (Multidrug resistance protein 1-MRP1) in the Polish population.
abstract: BACKGROUND
  Multidrug resistance-associated protein 1 (MRP1), encoded by the ABCC1 gene, is an ATP-binding cassette transporter mediating efflux of organic anions and xenobiotics; its overexpression leads to multidrug resistance. In this study, 30 exons (from 31 in total) of the ABCC1 gene as well as and their flanking intron sequences were screened for genetic variation, using the High Resolution Melting (HRM) method, for 190 healthy volunteers representing the Polish population. Polymorphism screening is an indispensable step in personalized patient therapy. An additional targeted SNP verification study for ten variants was performed to verify sensitivity of the scanning method.
  
  
  RESULTS
  During scanning, 46 polymorphisms, including seven novel ones, were found: one in 3' UTR, 21 in exons (11 of them non-synonymous) and 24 in introns, including one deletion variant. These results revealed some ethnic differences in frequency of several polymorphisms when compared to literature data for other populations. Based on linkage disequilibrium analysis, 4 haplotype blocks were determined for 9 detected polymorphisms and 12 haplotypes were defined. To capture the common haplotypes, haplotype-tagging single nucleotide polymorphisms were identified.
  
  
  CONCLUSIONS
  Targeted genotyping results correlated well with scanning results; thus, HRM is a suitable method to study genetic variation in this model. HRM is an efficient and sensitive method for scanning and genotyping polymorphic variants. Ethnic differences were found for frequency of some variants in the Polish population compared to others. Thus, this study may be useful for pharmacogenetics of drugs affected by MRP1-mediated efflux.
authors.affiliation: Biobank Lab, Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Łódź, Pilarskiego 14/16, 90-231, Łódź, Poland. m.slomka@biol.uni.lodz.pl.
authors.forename: Marcin
authors.initials: M
authors.lastname: Słomka
authors.affiliation: Biobank Lab, Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Łódź, Pilarskiego 14/16, 90-231, Łódź, Poland. sobalska@biol.uni.lodz.pl.
authors.forename: Marta
authors.initials: M
authors.lastname: Sobalska-Kwapis
authors.affiliation: Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106, 93-232, Łódź, Poland. mkorycka@cbm.pan.pl.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Korycka-Machała
authors.affiliation: Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Łódź, Pomorska 141/143, 90-236, Łódź, Poland. gbartosz@biol.uni.lodz.pl.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Bartosz
authors.affiliation: Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106, 93-232, Łódź, Poland. jdziadek@cbm.pan.pl.
authors.forename: Jarosław
authors.initials: J
authors.lastname: Dziadek
authors.affiliation: Biobank Lab, Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Łódź, Pilarskiego 14/16, 90-231, Łódź, Poland. strapag@biol.uni.lodz.pl.
authors.forename: Dominik
authors.initials: D
authors.lastname: Strapagiel
mesh_terms: D004252:DNA Mutational Analysis; D005787:Gene Frequency; D006801:Humans; D015810:Linkage Disequilibrium; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D011044:Poland; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012463:Saliva / Q000737:chemistry; D044465:White People / Q000235:genetics*
chemical_list: D027425:ATP-Binding Cassette, Sub-Family C Proteins; C421109:multidrug resistance-associated protein 1