Linked Life Data

18180275

Source:http://linkedlifedata.com/resource/pubmed/id/18180275

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-3-24
pubmed:abstractText
The hypothesis was tested that sequence diversity in breast cancer resistance protein (BCRP)'s cis-regulatory region is a significant determinant of BCRP expression. The BCRP promoter and intron 1 were resequenced in lymphoblast DNA from the polymorphism discovery resource (PDR) 44 subset. BCRP single nucleotide polymorphisms (SNPs) were genotyped in donor human livers, intestines, and lymphoblasts quantitatively phenotyped for BCRP mRNA expression. Carriers of the -15622C>T SNP had lower BCRP expression in multiple tissues. The intron 1 SNP 16702C>T was associated with high expression in livers; 1143G>A was associated with low expression in intestine; 12283T>C was associated with higher expression in the PDR44 and White livers. The -15994C>T promoter SNP was significantly associated with higher BCRP expression in multiple tissues. Patients with the -15994C>T genotype had substantially higher clearance of p.o. imatinib. We next determined whether BCRP expression was related to polymorphic alternative splicing or alternative promoter use. Liver polymorphically expressed an alternatively spliced mRNA [splice variant (SV) 1] skipping exon 2. Although SV1+ livers did not uniformly carry the exon 2 G34A allele, 90% of G34A livers expressed SV1 (versus 4% of 34GG livers). BCRP mRNA was significantly lower among Hispanic livers with the G34A variant genotype and may be due, in part, to polymorphic exon 2 splicing. Analysis of allele expression imbalance (AEI) showed that PDR44 samples with AEI had lower BCRP mRNA expression; however, no linked cis-polymorphisms were identified. BCRP used multiple promoters, and livers differentially using alternative exon 1b had lower BCRP. In conclusion, BCRP expression in lymphoblasts, liver, and intestine is associated with novel promoter and intron 1 SNPs.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1521-009X
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
780-95
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Association of breast cancer resistance protein/ABCG2 phenotypes and novel promoter and intron 1 single nucleotide polymorphisms.
pubmed:affiliation
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural