Buscar en
Medicina Clínica (English Edition)
Toda la web
Inicio Medicina Clínica (English Edition) Allelic and phenotypic characterization of CYP2D6 and its encoded P450 cytochrom...
Journal Information
Vol. 155. Issue 12.
Pages 529-534 (December 2020)
Share
Share
Download PDF
More article options
ePub
Visits
0
Vol. 155. Issue 12.
Pages 529-534 (December 2020)
Original article
Allelic and phenotypic characterization of CYP2D6 and its encoded P450 cytochrome enzyme in a serie of Spanish type 1 Gaucher disease patients
Caracterización alélica y fenotípica del gen y la enzima Cyp2d6 en una cohorte de pacientes españoles con enfermedad de Gaucher tipo 1
Visits
...
Laura López de Frutosa,b,
Corresponding author
llopezdefrutos.uit@gmail.com

Corresponding author.
, Pilar Alfonsoa, Carlos Lahoza,b, Pilar Irúnc, Pilar Giraldob
a Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain
b Fundación para el Estudio y la Terapéutica de la Enfermedad de Gaucher y Otras Lisosomales (FEETEG), Zaragoza, Spain
c Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), IIS Aragón, Zaragoza, Spain
Article information
Abstract
Full Text
Bibliography
Download PDF
Statistics
Figures (2)
Tables (2)
Table 1. GBA1 genotypes in our sample. GBA1 genotype frequency. Compound heterozygous with the variants NM_000157.3:c.1226A>G and c.1448T>C is the most common, follow by the homozygous state for the variant NM_000157.3:c.1226A>G. Other 30 variants have been found on combination with the c.1226A>G, half of it only has been observed in one patient.
Table 2. CYP2D6 variants distribution. Frequency of each analyzed variant on CYP2D6 in our population. Not all variants define an allele and some alleles need more than one variant to be defined.
Show moreShow less
Abstract
Background

Cytochrome p450 is the main drug metabolic pathway. CYP2D6 is a highly polymorphic gene that encodes a cytochrome p450 enzyme with three activity levels: null, reduced and normal. Apart from another type of mutations CYP2D6 can suffer duplications and deletions of the entire gene. This is the pathway to metabolize one of the Gaucher disease treatments, whose dose administration is regulated according to the metabolizer phenotype, this being one of the administration limitations.

Objectives

The aim of this paper is to evaluate the allelic frequencies and the metabolizer status of Gaucher type 1 patients in the Spanish population and compare it with the general Spanish population and other Gaucher disease groups.

Methods

In this study, 109 type 1 Gaucher disease patients were analyzed with the xTAG®CYP2D6 kit to identify the CYP2D6 gene alleles.

Results

We observed that eighty-seven patients could be classified as extensive, 14 as intermediate, 6 as poor and 2 as ultra-rapid metabolizers. The allelic duplication frequency is 5.5% and deletion is 4.5%. The most common allele is wild-type and the second is the null *4 allele. Intermediate phenotype frequency is higher than expected (p<0.05).

Conclusions

Our Spanish GD series shows an unexpected distribution of some alleles and phenotypic metabolizer status, in contrast to that previously reported in the Spanish population.

Keywords:
Type 1 Gaucher disease
CYP2D6 gene
P450 cytochrome
Spanish genotype
Abbreviations:
CYPIID6
PharmVar
NM
IM
PM
UM
AS
GD
GD1
Gb1
SRT
CG1
CG2
Resumen
Introducción

La superfamilia citocromo P450 es la principal vía de metabolización de fármacos. Uno de los genes que la componen, CYP2D6, es altamente polimórfico y puede producir enzimas con 3 niveles de actividad: nula, reducida o normal. Además de presentar variantes puntuales, este gen puede sufrir duplicidad o deleción. CYP2D6 es la principal vía de metabolización del último tratamiento aprobado para la enfermedad de Gaucher, cuya administración y dosificación depende del estado metabolizador de CYP2D6.

Objetivos

El objetivo de este trabajo es evaluar la frecuencia alélica y la distribución de fenotipos metabolizadores en una serie de pacientes españoles con enfermedad de Gaucher, y compararla con los datos publicados para población española general y con otros grupos de pacientes de Gaucher.

Métodos

Se han genotipificado 109 pacientes con enfermedad de Gaucher tipo 1 mediante el sistema xTAG® CYP2D6.

Resultados

Nuestra población se distribuye en 87 pacientes con un fenotipo metabolizador normal, 14 intermedios, 6 lentos y 2 ultrarrápidos. La frecuencia de la duplicación y deleción del gen es del 5,5 y 4,5%, respectivamente. El alelo más común es la forma nativa de la proteína y el segundo el alelo *4 que codifica para una proteína inactiva. La frecuencia de fenotipos intermedios es superior a la esperada en población general (p<0,05), principalmente a causa de un incremento en la frecuencia de los alelos que codifican enzimas con actividad reducida (p<0,05).

Conclusiones

El grupo español de pacientes con enfermedad de Gaucher muestra una distribución alélica y fenotípica diferente a la esperada para la población española.

Palabras clave:
Enfermedad de Gaucher tipo 1
Gen CYP2D6
Citocromo P450
CYP450 genotipo población española

Article

These are the options to access the full texts of the publication Medicina Clínica (English Edition)
Subscriber
Subscriber

If you already have your login data, please click here .

If you have forgotten your password you can you can recover it by clicking here and selecting the option “I have forgotten my password”
Subscribe
Subscribe to

Medicina Clínica (English Edition)

Purchase
Purchase article

Purchasing article the PDF version will be downloaded

Price 19.34 €

Purchase now
Contact
Phone for subscriptions and reporting of errors
From Monday to Friday from 9 a.m. to 6 p.m. (GMT + 1) except for the months of July and August which will be from 9 a.m. to 3 p.m.
Calls from Spain
932 415 960
Calls from outside Spain
+34 932 415 960
E-mail
Article options
Tools
es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos