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Effect of the PPARα-activator gemfibrozil on whole blood drug transporter gene expression in humans

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dc.date.accessioned 2014-06-09T18:34:39Z
dc.date.accessioned 2015-07-29T08:40:45Z
dc.date.available 2014-06-09T18:34:39Z
dc.date.available 2015-07-29T08:40:45Z
dc.date.issued 2014-06-09T18:34:39Z
dc.identifier.uri http://hdl.handle.net/10138.1/3777
dc.title Effect of the PPARα-activator gemfibrozil on whole blood drug transporter gene expression in humans en
ethesis.discipline Pharmacology en
ethesis.discipline Farmakologia fi
ethesis.discipline Farmakologi sv
ethesis.discipline.URI http://data.hulib.helsinki.fi/id/28b74762-6d0b-485e-b81b-574f23530d0e
ethesis.department Biomedicinska institutionen sv
ethesis.department Institute of Biomedicine en
ethesis.department Biolääketieteen laitos fi
ethesis.faculty Faculty of Medicine en
ethesis.faculty Medicinska fakulteten sv
ethesis.faculty Lääketieteellinen tiedekunta fi
ethesis.faculty.URI http://data.hulib.helsinki.fi/id/a4d5aaa2-b5aa-41a7-ba4c-e5e0df7a902d
ethesis.university.URI http://data.hulib.helsinki.fi/id/50ae46d8-7ba9-4821-877c-c994c78b0d97
ethesis.university Helsingfors universitet sv
ethesis.university University of Helsinki en
ethesis.university Helsingin yliopisto fi
dct.creator Miao, Zefeng
dct.issued 2014
dct.language.ISO639-2 eng
dct.abstract Gemfibrozil is a fibric acid derivative used in the treatment of dyslipidemia. It activates peroxisome proliferator activated receptor α (PPARα) and alters lipoprotein metabolism gene expression. PPARα may also regulate the expression of drug disposition genes (e.g., CYP3A4). The aim of this study was to investigate possible effects of gemfibrozil on drug transporter gene expression in human whole blood. In a randomized crossover study, 10 healthy volunteers took 600 mg gemfibrozil or placebo twice daily for 6 days (Filppula et al. 2013). On the morning of day 3, a venous blood RNA sample was collected from each participant into a PaxGene® tube. The expression of 18 ABC, 24 SLC and 10 SLCO transporters was investigated using reverse transcription quantitative real-time PCR (RT-qPCR) with OpenArray® technology on a QuantStudio™ 12 K Flex Real-Time PCR system (Life Technologies, Paisley, UK). FPGS, TRAP1, DECR1 and PPIB served as reference genes. A total of 31 transporters, including 15 ABC transporters, 13 SLC transporters and 3 SLCO transporters were significantly expressed in whole blood during the placebo phase. Gemfibrozil appeared to alter the expression of three transporters. The expression of SLCO3A1 was increased by 34% by gemfibrozil (P=0.004), but gemfibrozil reduced the expression of ABCG2 and ABCC3 by 31% (P=0.018) and 50% (P=0.045), respectively. However, none of the differences remained statistically significant after correction for multiple testing. In conclusion, these data suggest that gemfibrozil might alter the gene expression of certain drug transporters in human blood. en
dct.language en
ethesis.language.URI http://data.hulib.helsinki.fi/id/languages/eng
ethesis.language English en
ethesis.language englanti fi
ethesis.language engelska sv
ethesis.supervisor Niemi, Mikko Jr
ethesis.thesistype pro gradu-avhandlingar sv
ethesis.thesistype pro gradu -tutkielmat fi
ethesis.thesistype master's thesis en
ethesis.thesistype.URI http://data.hulib.helsinki.fi/id/thesistypes/mastersthesis
dct.identifier.urn URN:NBN:fi:hulib-201507282597
dc.type.dcmitype Text
ethesis-internal.updated TRUE2

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