Low frequency of defective alleles of cytochrome P450 enzymes 2C19 and 2D6in the Turkish population

Citation
As. Aynacioglu et al., Low frequency of defective alleles of cytochrome P450 enzymes 2C19 and 2D6in the Turkish population, CLIN PHARM, 66(2), 1999, pp. 185-192
Citations number
41
Categorie Soggetti
Pharmacology,"Pharmacology & Toxicology
Journal title
CLINICAL PHARMACOLOGY & THERAPEUTICS
ISSN journal
00099236 → ACNP
Volume
66
Issue
2
Year of publication
1999
Pages
185 - 192
Database
ISI
SICI code
0009-9236(199908)66:2<185:LFODAO>2.0.ZU;2-9
Abstract
Background and objectives: The genetically polymorphic cytochrome P450 enzy mes 2C19 (CYP2C19) and 2D6 (CYP2D6) contribute to the metabolism of about 3 0% of all drugs. I:or analysis of the ethnic-related differences in drug di sposition and as a preparation for routine genotyping, we examined CYP2C19 and CYP2D6 mutations in a large Turkish population. Methods: CYP2C19 and CYP2D6 alleles were determined with use of genomic deo xyribonucleic acid from 404 unrelated Turkish individuals. CYP2C19 alleles *1 to *5 and CYP2D6 alleles *1 to *12 and *14, *15, and *17 were measured b y polymerase chain reaction-restriction fragment length polymorphism assays . Results: From 404 subjects genotyped for CYP2C19, allele frequencies of: CY P2C19*1 (wt), CYP2C19*2 (ml), and CYP2C19*3 (m2) were 0.88, 0.12, and 0.004 , respectively; mutations m3 and m4 were not found. Pour individuals (1.0%) were predicted to be poor metabolizers (CYP2C19*2/*2), a significantly low er frequency compared to Middle European populations. Among 404 subjects ge notyped for CYP2D6 most frequent alleles were CYP2D6*1 (allele frequency 0. 37), *2(0.35), *4(0.11), *10(0.06), duplications *1x2, *2x2, or *4x2(0.06), *5(0.01), and *17(0.01). Overall, six subjects (1.49%) were predicted to b e CYP2D6 poor metabolizers, and 35 subjects (8.66%) were predicted to be ul trarapid metabolizers as a result of CYP2D6 gene duplications. Conclusion: Obviously, within Europe there is a north-south gradient, with decreasing frequency of poor metabolizers of CYP2C19 and CYP2D6 to the sout h and a corresponding increase of ultrarapid metabolizers of CYP2D6. As in other white groups, only CYP2C19*2 plays a relevant role for the CYP2C19 po or metabolizer phenotype. The mutational spectrum of CYP2D6 indicated parti al ethnic relationships to Asian and African populations.