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| Polymorphismen in der Promoter- und Enhancerregion von CYP3A4 Stoffels, Felix |
| Main title | Polymorphismen in der Promoter- und Enhancerregion von CYP3A4 |
| Title variations | Polymorphisms in the promoter and enhancer region of CYP3A4 |
| Author(s) | Stoffels, Felix
Place of birth: Hamburg, Deutschland |
| 1. Referee | Prof. Dr. med. I. Roots |
| Further Referee(s) | Prof. Dr. med. J. Brockmöller Prof. Dr. H.-J. Rommelspacher |
| Keywords | CYP3A4; promoter; enhancer; polymorphism; alprazolam |
| Classification (DDC) | 610 Medical sciences; Medicine |
| Summary | In this study the activity of CYP3A4 was measured at 104 healthy european subjects by the degradation of alprazolam through the enzyme before and after induction ba rifampicin. Afterwards the promoter and enhancer region of the enzyme was sequenced and the correlation between the polymorphisms in this region and the basal and induced activity were analyzed. There were no polymorphisms found in the enhancer region. In the promoter region we found the SNPs CYP3A4*1B and CYP3A4*1F. Further known or unknown polymorphisms were not detected. The allel frequency of CYP3A4*1B was 2.4%. This polymorphism had no influence to the activity of the enzyme neither before nor after induction. CYP3A4*1F was measured with an allel frequency of 5.3%. It had as well no relevant influence on the degradation of alprazolam by the enzyme. CYP3A4*1F leads to a new CpG island. This was both in the leucocytes of the tested subjects and in seven additionally tested liver probes fully methylized. This result shows that the promoter and enhancer region of CYP3A4 has a high relevance for the function of this enzyme and therefore it is highly conserved through evolution. Furthermore this study shows that the methylation of CpGs is a quite unspecific process, because even new appearing potential methylation positions are fully methylized. |
| Documents |
Dataobject from FUDISS_thesis_000000014960
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| FU Department | Department of Medicine - Charité - University Medicine Berlin |
| Year of publication | 2010 |
| Document type | Doctoral thesis |
| Media type/Format | Text |
| Language | German |
| Terms of use/Rights | Nutzungsbedingungen |
| Date of defense | 2010-01-29 |
| Created at | 2009-12-21 : 08:20:55 |
| Last changed | 2010-02-19 : 12:24:20 |
| Static URL | http://www.diss.fu-berlin.de/diss/receive/FUDISS_thesis_000000014960 |
| NBN | urn:nbn:de:kobv:188-fudissthesis000000014960-8 |
| Statistics | |
| E-mail address | 1festo@gmx.net |
