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.
TY - 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 . .
