Functional characterization of CYP2D7 gene variants.
Pharmacogenomics
; 19(12): 931-936, 2018 08 01.
Article
en En
| MEDLINE
| ID: mdl-30040020
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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Variación Genética
/
Sistema Enzimático del Citocromo P-450
Límite:
Humans
Idioma:
En
Revista:
Pharmacogenomics
Asunto de la revista:
FARMACOLOGIA
/
GENETICA MEDICA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Suecia