Allelic and phenotypic characterization of CYP2D6 and its encoded P450 cytochrome enzyme in a serie of Spanish type 1 Gaucher disease patients

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 (R) 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. (C) 2020 Elsevier Espana, S.L.U. All rights reserved.