Functional characterization of CYP2D7 gene variants
Samo za registrovane korisnike
2018
Autori
Jukić, MarinLauschke, Volker M.
Saito, Takahiro
Hiratsuka, Masahiro
Ingelman-Sundberg, Magnus
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
The ultrarapid CYP2D6 metabolizer (UM) phenotype is caused by CYP2D6 gene duplications in some, but not all, UM individuals. CYP2D6 and the adjacent pseudogene CYP2D7 are highly homologous; however, CYP2D7 harbors a premature stop codon, which is absent in carriers of the rare CYP2D7 variant rs530303678. We addressed whether rs530303678 could generate a functionally active protein, causing the UM phenotype. However, unlike CYP2D6 variants, two CYP2D7 rs530303678 variant isoforms, previously described in liver, showed neither significant protein expression nor catalytic activity toward the CYP2D6 substrates bufuralol or dextromethorphan. We conclude that loss of the stop codon in CYP2D7 does not result in the generation of enzymatically active protein in human liver and thus, cannot cause the UM phenotype.
Ključne reči:
CYP2D6 / ultrarapid metabolizam / CYP2D7 / bufuralol / dextromethorphanIzvor:
Pharmacogenomics, 2018, 19, 12, 931-936Izdavač:
- Future Medicine Ltd, London
Finansiranje / projekti:
- Swedish Research Council - 2015-02760
DOI: 10.2217/pgs-2018-0065
ISSN: 1462-2416
PubMed: 30040020
WoS: 000445669500002
Scopus: 2-s2.0-85051123698
Institucija/grupa
PharmacyTY - JOUR AU - Jukić, Marin AU - Lauschke, Volker M. AU - Saito, Takahiro AU - Hiratsuka, Masahiro AU - Ingelman-Sundberg, Magnus PY - 2018 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3200 AB - The ultrarapid CYP2D6 metabolizer (UM) phenotype is caused by CYP2D6 gene duplications in some, but not all, UM individuals. CYP2D6 and the adjacent pseudogene CYP2D7 are highly homologous; however, CYP2D7 harbors a premature stop codon, which is absent in carriers of the rare CYP2D7 variant rs530303678. We addressed whether rs530303678 could generate a functionally active protein, causing the UM phenotype. However, unlike CYP2D6 variants, two CYP2D7 rs530303678 variant isoforms, previously described in liver, showed neither significant protein expression nor catalytic activity toward the CYP2D6 substrates bufuralol or dextromethorphan. We conclude that loss of the stop codon in CYP2D7 does not result in the generation of enzymatically active protein in human liver and thus, cannot cause the UM phenotype. PB - Future Medicine Ltd, London T2 - Pharmacogenomics T1 - Functional characterization of CYP2D7 gene variants VL - 19 IS - 12 SP - 931 EP - 936 DO - 10.2217/pgs-2018-0065 ER -
@article{ author = "Jukić, Marin and Lauschke, Volker M. and Saito, Takahiro and Hiratsuka, Masahiro and Ingelman-Sundberg, Magnus", year = "2018", abstract = "The ultrarapid CYP2D6 metabolizer (UM) phenotype is caused by CYP2D6 gene duplications in some, but not all, UM individuals. CYP2D6 and the adjacent pseudogene CYP2D7 are highly homologous; however, CYP2D7 harbors a premature stop codon, which is absent in carriers of the rare CYP2D7 variant rs530303678. We addressed whether rs530303678 could generate a functionally active protein, causing the UM phenotype. However, unlike CYP2D6 variants, two CYP2D7 rs530303678 variant isoforms, previously described in liver, showed neither significant protein expression nor catalytic activity toward the CYP2D6 substrates bufuralol or dextromethorphan. We conclude that loss of the stop codon in CYP2D7 does not result in the generation of enzymatically active protein in human liver and thus, cannot cause the UM phenotype.", publisher = "Future Medicine Ltd, London", journal = "Pharmacogenomics", title = "Functional characterization of CYP2D7 gene variants", volume = "19", number = "12", pages = "931-936", doi = "10.2217/pgs-2018-0065" }
Jukić, M., Lauschke, V. M., Saito, T., Hiratsuka, M.,& Ingelman-Sundberg, M.. (2018). Functional characterization of CYP2D7 gene variants. in Pharmacogenomics Future Medicine Ltd, London., 19(12), 931-936. https://doi.org/10.2217/pgs-2018-0065
Jukić M, Lauschke VM, Saito T, Hiratsuka M, Ingelman-Sundberg M. Functional characterization of CYP2D7 gene variants. in Pharmacogenomics. 2018;19(12):931-936. doi:10.2217/pgs-2018-0065 .
Jukić, Marin, Lauschke, Volker M., Saito, Takahiro, Hiratsuka, Masahiro, Ingelman-Sundberg, Magnus, "Functional characterization of CYP2D7 gene variants" in Pharmacogenomics, 19, no. 12 (2018):931-936, https://doi.org/10.2217/pgs-2018-0065 . .