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WFRF:(Hesselson Stephanie E.)
 

Sökning: WFRF:(Hesselson Stephanie E.) > Genetic variation i...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00003853naa a2200565 4500
001oai:DiVA.org:uu-151834
003SwePub
008110418s2009 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1518342 URI
0247 a https://doi.org/10.1371/journal.pone.00069422 DOI
040 a (SwePub)uu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Hesselson, Stephanie E4 aut
2451 0a Genetic variation in the proximal promoter of ABC and SLC superfamilies :b liver and kidney specific expression and promoter activity predict variation
264 c 2009-09-09
264 1b Public Library of Science (PLoS),c 2009
338 a print2 rdacarrier
500 a De fyra första författarna delar förstaförfattarskapet
520 a Membrane transporters play crucial roles in the cellular uptake and efflux of an array of small molecules including nutrients, environmental toxins, and many clinically used drugs. We hypothesized that common genetic variation in the proximal promoter regions of transporter genes contribute to observed variation in drug response. A total of 579 polymorphisms were identified in the proximal promoters (-250 to +50 bp) and flanking 5' sequence of 107 transporters in the ATP Binding Cassette (ABC) and Solute Carrier (SLC) superfamilies in 272 DNA samples from ethnically diverse populations. Many transporter promoters contained multiple common polymorphisms. Using a sliding window analysis, we observed that, on average, nucleotide diversity (pi) was lowest at approximately 300 bp upstream of the transcription start site, suggesting that this region may harbor important functional elements. The proximal promoters of transporters that were highly expressed in the liver had greater nucleotide diversity than those that were highly expressed in the kidney consistent with greater negative selective pressure on the promoters of kidney transporters. Twenty-one promoters were evaluated for activity using reporter assays. Greater nucleotide diversity was observed in promoters with strong activity compared to promoters with weak activity, suggesting that weak promoters are under more negative selective pressure than promoters with high activity. Collectively, these results suggest that the proximal promoter region of membrane transporters is rich in variation and that variants in these regions may play a role in interindividual variation in drug disposition and response.
7001 a Matsson, Päru Uppsala universitet,Institutionen för farmaci4 aut0 (Swepub:uu)pamat517
7001 a Shima, James E4 aut
7001 a Fukushima, Hisayo4 aut
7001 a Yee, Sook Wah4 aut
7001 a Kobayashi, Yuya4 aut
7001 a Gow, Jason M4 aut
7001 a Ha, Connie4 aut
7001 a Ma, Benjamin4 aut
7001 a Poon, Annie4 aut
7001 a Johns, Susan J4 aut
7001 a Stryke, Doug4 aut
7001 a Castro, Richard A4 aut
7001 a Tahara, Harunobu4 aut
7001 a Choi, Ji Ha4 aut
7001 a Chen, Ligong4 aut
7001 a Picard, Nicolas4 aut
7001 a Sjödin, Elin4 aut
7001 a Roelofs, Maarke J E4 aut
7001 a Ferrin, Thomas E4 aut
7001 a Myers, Richard4 aut
7001 a Kroetz, Deanna L4 aut
7001 a Kwok, Pui-Yan4 aut
7001 a Giacomini, Kathleen M4 aut
7102 a Uppsala universitetb Institutionen för farmaci4 org
7730 t PLOS ONEd : Public Library of Science (PLoS)g 4:9, s. e6942-q 4:9<e6942-x 1932-6203
8564 u https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0006942&type=printable
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-151834
8564 8u https://doi.org/10.1371/journal.pone.0006942

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