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
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.