Chen, Jiayin

[["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Biological Chemistry"],["dc.bibliographiccitation.volume","398"],["dc.contributor.author","Chen, Jiayin"],["dc.contributor.author","Brockmoeller, Juergen"],["dc.contributor.author","Seitz, Tina"],["dc.contributor.author","Koenig, Joerg"],["dc.contributor.author","Tzvetkov, Mladen Vassilev"],["dc.contributor.author","Chen, Xijing"],["dc.date.accessioned","2018-11-07T10:22:22Z"],["dc.date.available","2018-11-07T10:22:22Z"],["dc.date.issued","2017"],["dc.format.extent","813"],["dc.identifier.doi","10.1515/hsz-2017-0129"],["dc.identifier.isi","000403093600009"],["dc.identifier.pmid","28291733"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42256"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Walter De Gruyter Gmbh"],["dc.relation.issn","1437-4315"],["dc.relation.issn","1431-6730"],["dc.title","Tropane alkaloids as substrates and inhibitors of human organic cation transporters of the SLC22 (OCT) and the SLC47 (MATE) families (vol 398, pg 237, 2017)"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","56"],["dc.bibliographiccitation.journal","Genome Medicine"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Seitz, Tina"],["dc.contributor.author","Stalmann, Robert"],["dc.contributor.author","Dalila, Nawar"],["dc.contributor.author","Chen, Jiayin"],["dc.contributor.author","Pojar, Sherin"],["dc.contributor.author","Pereira, Joao N. dos Santos"],["dc.contributor.author","Kraetzner, Ralph"],["dc.contributor.author","Brockmoeller, Juergen"],["dc.contributor.author","Tzvetkov, Mladen Vassilev"],["dc.date.accessioned","2018-11-07T09:55:48Z"],["dc.date.available","2018-11-07T09:55:48Z"],["dc.date.issued","2015"],["dc.description.abstract","Background: The organic cation transporter OCT1 (SLC22A1) mediates the uptake of vitamin B1, cationic drugs, and xenobiotics into hepatocytes. Nine percent of Caucasians lack or have very low OCT1 activity due to loss-of-function polymorphisms in OCT1 gene. Here we analyzed the global genetic variability in OCT1 to estimate the therapeutic relevance of OCT1 polymorphisms in populations beyond Caucasians and to identify evolutionary patterns of the common loss of OCT1 activity in humans. Methods: We applied massively parallel sequencing to screen for coding polymorphisms in 1,079 unrelated individuals from 53 populations worldwide. The obtained data was combined with the existing 1000 Genomes data comprising an additional 1,092 individuals from 14 populations. The identified OCT1 variants were characterized in vitro regarding their cellular localization and their ability to transport 10 known OCT1 substrates. Both the population genetics data and transport data were used in tandem to generate a world map of loss of OCT1 activity. Results: We identified 16 amino acid substitutions potentially causing loss of OCT1 function and analyzed them together with five amino acid substitutions that were not expected to affect OCT1 function. The variants constituted 16 major alleles and 14 sub-alleles. Six major alleles showed improper subcellular localization leading to substrate-wide loss in activity. Five major alleles showed correct subcellular localization, but substrate-specific loss of activity. Striking differences were observed in the frequency of loss of OCT1 activity worldwide. While most East Asian and Oceanian individuals had completely functional OCT1, 80 % of native South American Indians lacked functional OCT1 alleles. In East Asia and Oceania the average nucleotide diversity of the loss-of-function variants was much lower than that of the variants that do not affect OCT1 function (ratio of 0.03) and was significantly lower than the theoretically expected heterozygosity (Tajima's D=-1.64, P < 0.01). Conclusions: Comprehensive genetic analyses showed strong global variations in the frequency of loss of OCT1 activity with selection pressure for maintaining OCT1 activity in East Asia and Oceania. These results not only enable pharmacogenetically-based optimization of drug treatment worldwide, but may help elucidate the functional role of human OCT1."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2015"],["dc.identifier.doi","10.1186/s13073-015-0172-0"],["dc.identifier.isi","000357566500001"],["dc.identifier.pmid","26157489"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13466"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36829"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1756-994X"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Global genetic analyses reveal strong inter-ethnic variability in the loss of activity of the organic cation transporter OCT1"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","237"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Biological Chemistry"],["dc.bibliographiccitation.lastpage","249"],["dc.bibliographiccitation.volume","398"],["dc.contributor.author","Chen, Jiayin"],["dc.contributor.author","Brockmoeller, Juergen"],["dc.contributor.author","Seitz, Tina"],["dc.contributor.author","Koenig, Joerg"],["dc.contributor.author","Tzvetkov, Mladen Vassilev"],["dc.contributor.author","Chen, Xijing"],["dc.date.accessioned","2018-11-07T10:28:12Z"],["dc.date.available","2018-11-07T10:28:12Z"],["dc.date.issued","2017"],["dc.description.abstract","Tropane alkaloids and their derivatives are anticholinergic drugs with narrow therapeutic range. Here we characterize the organic cation transporters from the SLC22 (OCT1, OCT2, and OCT3) and the SLC47 families (MATE1 and MATE2-K) as potential mediators of the renal and extra-renal excretion, the two major roads of elimination of these substances. All analyzed compounds inhibited and the quaternary amine derivatives ipratropium and trospium were strongly transported by OCTs and MATEs. Overexpression of OCTs or MATEs in HEK293 cells resulted in an up to 63-fold increase in the uptake of ipratropium (K-m of 0.32 mu m to OCT2 and V-max of 3.34 nmol x mg protein(-1) x min(-1) to MATE1). The transcellular transport of ipratropium was 16-fold higher in OCT2-MATE1 and 10-fold higher in OCT1-MATE1 overexpressing compared to control MDCKII cells. Genetic polymorphisms in OCT1 and OCT2 affected ipratropium uptake and clinically relevant concentration of ondansetron and pyrithiamine inhibited ipratropium uptake via MATEs by more than 90%. This study suggests that OCT1, OCT2 and MATEs may be strongly involved in the renal and extra-renal elimination of ipratropium and other quaternary amine alkaloids. These substances have a notoriously narrow therapeutic range and the drug-drug interactions suggested here should be further critically evaluated in humans."],["dc.identifier.doi","10.1515/hsz-2016-0236"],["dc.identifier.isi","000391201600009"],["dc.identifier.pmid","27676604"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43371"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Walter De Gruyter Gmbh"],["dc.relation.issn","1437-4315"],["dc.relation.issn","1431-6730"],["dc.title","Tropane alkaloids as substrates and inhibitors of human organic cation transporters of the SLC22 (OCT) and the SLC47 (MATE) families"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]