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Characterization of the CYP2D6 drug metabolizing phenotypes of the Chilean mestizo population through polymorphism analyses.
- Source :
-
Pharmacological Research . Nov2015, Vol. 101, p124-129. 6p. - Publication Year :
- 2015
-
Abstract
- We tested the influence of four polymorphisms and gene duplication in CYP2D6 on in vivo enzyme activity in a Chilean mestizo population in order to identify the most relevant genetic profiles that account for observed phenotypes in this ethnic group. CYP2D6 *2 (2850C>T), *3 (2549A>del), *4 (1846G>A), *17 (1023C>T) and gene duplication were determined by PCR-RFLP or PCRL in a group of 321 healthy volunteers. Individuals with different variant alleles were phenotyped by determining debrisoquine 4-hydroxylase activity as a metabolic ratio (MR) using a validated HPLC assay. Minor allele frequencies were 0.41, 0.01, 0.12 and 0.00 for CYP2D6 *2, *3, *4 and *17 variants, respectively, and the duplication frequency was 0.003. Genotype analysis correlated with phenotypes in 18 of 23 subjects (78.3%). 11 subjects were extensive metabolizers (EM), 8 were intermediate metabolizers (IM), 2 were poor metabolizers (PM) and 2 were ultra-rapid metabolizers (UM) which is fairly coincident with expected phenotypes metabolic ratios ranged from 0.11 to 126.41. The influence of CYP2D6 *3 was particularly notable, although only heterozygote carriers were present in our population. Individuals homozygous for *4 were always PM. As expected, the only subject with gene duplication was UM. In conclusion, there was a clear effect of genotype on observed CYP2D6 activity. Classification of EM, PM and UM through genotyping was useful to characterize CYP2D6 phenotype in the Chilean mestizo population. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10436618
- Volume :
- 101
- Database :
- Academic Search Index
- Journal :
- Pharmacological Research
- Publication Type :
- Academic Journal
- Accession number :
- 110475588
- Full Text :
- https://doi.org/10.1016/j.phrs.2015.07.020