The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.
Natural allelic variants of breast cancer resistance protein (BCRP) and their relationship to BCRP expression in human intestine
Abstract
The aim of this study was to identify the extent of genetic variability in breast cancer resistance protein (BCRP) in humans. We first analysed the sequence of BCRP cDNA from human livers and from human intestines phenotyped for expression of intestinal BCRP. We then determined the frequency of all known coding single nucleotide polymorphisms (cSNPs) using DNA from individuals representing 11 different ethnic populations. Nine SNPs including four non-synonymous and three synonymous cSNPs and two intronic SNPs were identified. Of the missense mutations, exon 2 SNP (G34A) resulted in a V12M change; exon 5 SNP (C421A) resulted in a Q141K substitution; exon 6 SNP (A616C) resulted in an I206L amino acid substitution; and exon 15 SNP (A1768T) resulted in a N590Y change in the BCRP protein. The two most frequent polymorphisms identified in the human population studied were the G34A and C421A transitions. There was marked variation in BCRP genotypes and allele frequencies in the different populations. BCRP mRNA was phenotyped in human small bowel intestinal samples by real-time polymerase chain reaction and BCRP protein was analysed on immunoblots of tissue from the same individuals. There was a 78-fold variation in expression of BCRP mRNA and significant variation in BCRP protein expression in human intestine. Expression of intestinal BCRP mRNA and protein was not different between persons expressing the common Gln141 allele compared to the Lys141 allele. Thus, common natural allelic variants of BCRP have been identified, and did not influence interindividual variation in expression of BCRP mRNA in human intestine, but remain to be tested for their effect on BCRP function.
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Cited by
Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2)
Austin Doyle, L., & Ross, D. D. (2003) · Oncogene · doi:10.1038/sj.onc.1206938 · Cited by 1,051
Gut instincts: Explorations in intestinal physiology and drug delivery
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Role of the breast cancer resistance protein (ABCG2) in drug transport
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The Role of Ethnicity in Variability in Response to Drugs: Focus on Clinical Pharmacology Studies
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Metadata
- Authors
- Zamber, C. P., Lamba, J. K., Yasuda, K., Farnum, J., Thummel, K., Schuetz, J. D., & Schuetz, E. G.
- Venue
- Pharmacogenetics
- Published
- 2003-01
- Volume
- 13
- Issue
- 1
- Pages
- 19-28
- ISSN
- 0960-314X (ISSN-L)
- OpenAlex
- W2052209393
- Cited by
- 272
- References
- 26
- FWCI
- 10.38
- Type
- journal article
- Language
- en
- Open access
- closed
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- Zamber, C. P., Lamba, J. K., Yasuda, K., Farnum, J., Thummel, K., Schuetz, J. D., & Schuetz, E. G. (2003). Natural allelic variants of breast cancer resistance protein (BCRP) and their relationship to BCRP expression in human intestine. Pharmacogenetics. https://doi.org/10.1097/00008571-200301000-00004
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