Abstract
BackgroundMultidrug 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.ResultsDuring 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.ConclusionsTargeted 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-015-0271-3) contains supplementary material, which is available to authorized users.
Highlights
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
We focused on highly polymorphic regions of the ABCC1 gene existing in databases, often examined in recent publications
ABCC1 genetic variation detected in this study We screened coding regions and exon/intron boundaries as the most important gene areas (Additional file 1)
Summary
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. exons (from 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. The human multidrug resistance-associated protein 1 (MRP1) is a member of the ATP-binding cassette (ABC) transporter superfamily and is encoded by the ABCC1 gene [1]. High levels of MRP1 expression were detected in lung, kidney, heart, testis, placenta, adrenal glands and skeletal muscles, while lower levels of expression were found in intestine, colon, brain, peripheral blood mononuclear cells and liver [1, 3, 8]. With the exception of brain cells, MRP1, in contrast to other ABC transporters, is expressed at the basolateral membrane of polarized epithelial cells where it plays a protective role against xenobiotics and their metabolites [3, 9]
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