title: Genetic variation in the ATP-binding cassette transporter gene ABCG2 (BCRP) in a Swedish population.
abstract: The ATP-binding cassette transporter ABCG2 (also named breast cancer resistance protein, BCRP) functions as a drug efflux transporter and is expressed at high levels in the human small intestine. The aim of this study was to screen the human ABCG2 gene for genetic variation. The regions of the gene most likely to affect function, namely the coding parts, exon/intron boundaries, 5' untranslated region and 3' untranslated region and the proposed promoter region, were included in the screening. DNA was obtained from 60 Swedish individuals. The screening was performed using a polymerase chain reaction-denaturing high-performance liquid chromatography approach followed by sequence analysis. Eight sites of genetic variation were identified. The sequence variations considered to be most likely to affect transcription level or transport function were a CTCA deletion in the 5' flanking region, a single nucleotide polymorphism (SNP) in a 5' flanking CpG island, two non-synonymous SNPs, changing valine at amino acid position 12 to methionine and glutamine at position 141 to lysine, respectively. Genotyping of these sequence variations revealed linkage between the CTCA deletion and the SNP changing glutamine 141 for lysine. This information forms the basis for future association studies to investigate the genetic basis of differences of drug disposition due to sequence variation in the ABCG2 gene.
authors.affiliation: Department of Pharmacy, Uppsala University, P.O. Box 580, SE-751 23 Uppsala, Sweden.
authors.forename: Gunilla
authors.initials: G
authors.lastname: Bäckström
authors.forename: Jan
authors.initials: J
authors.lastname: Taipalensuu
authors.forename: Håkan
authors.initials: H
authors.lastname: Melhus
authors.forename: Helena
authors.initials: H
authors.lastname: Brändström
authors.forename: Ann-Cathrin
authors.initials: AC
authors.lastname: Svensson
authors.forename: Per
authors.initials: P
authors.lastname: Artursson
authors.forename: Andreas
authors.initials: A
authors.lastname: Kindmark
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D013548:Sweden
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D009363:Neoplasm Proteins