Low frequency of defective alleles of cytochrome P450 enzymes 2C19 and 2D6 in the Turkish population.

Bibliographic Collection: 
MOCA Reference, APE
Publication Type: Journal Article
Authors: Aynacioglu, A S; Sachse, C; Bozkurt, A; Kortunay, S; Nacak, M; Schröder, T; Kayaalp, S O; Roots, I; Brockmöller, J
Year of Publication: 1999
Journal: Clin Pharmacol Ther
Volume: 66
Issue: 2
Pagination: 185-92
Date Published: 08/1999
Publication Language: eng
ISSN: 0009-9236
Keywords: Adult, Alleles, Aryl Hydrocarbon Hydroxylases, Cytochrome P-450 CYP2C19, Cytochrome P-450 CYP2D6, Cytochrome P-450 Enzyme System, Europe, European Continental Ancestry Group, Female, Genotype, Humans, Incidence, Male, Mixed Function Oxygenases, Mutation, Polymerase Chain Reaction, Polymorphism, Restriction Fragment Length, Turkey

BACKGROUND AND OBJECTIVES: The genetically polymorphic cytochrome P450 enzymes 2Cl9 (CYP2Cl9) and 2D6 (CYP2D6) contribute to the metabolism of about 30% of all drugs. For analysis of the ethnic-related differences in drug disposition 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 deoxyribonucleic acid from 404 unrelated Turkish individuals. CYP2C19 alleles *1 to *5 and CYP2D6 alleles *1 to *12, and *14, *15, and *17 were measured by polymerase chain reaction-restriction fragment length polymorphism assays.

RESULTS: From 404 subjects genotyped for CYP2C19, allele frequencies of CYP2C19*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. Four individuals (1.0%) were predicted to be poor metabolizers (CYP2C19*2/*2), a significantly lower frequency compared to Middle European populations. Among 404 subjects genotyped 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 be CYP2D6 poor metabolizers, and 35 subjects (8.66%) were predicted to be ultrarapid 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 south and a corresponding increase of ultrarapid metabolizers of CYP2D6. As in other white groups, only CYP2C19*2 plays a relevant role for the CYP2C19 poor metabolizer phenotype. The mutational spectrum of CYP2D6 indicated partial ethnic relationships to Asian and African populations.

DOI: 10.1053/cp.1999.v66.100072001
Alternate Journal: Clin. Pharmacol. Ther.
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