Premium
Low frequency of defective alleles of cytochrome P450 enzymes 2C19 and 2D6 in the Turkish population
Author(s) -
Aynacioglu A. Sükrü,
Sachse Christoph,
Bozkurt Atilla,
Kortunay Selim,
Nacak Muradiye,
Schröder Thomas,
Kayaalp S. Oguz,
Roots Ivar,
Brockmöller Jürgen
Publication year - 1999
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1053/cp.1999.v66.100072001
Subject(s) - cyp2c19 , cyp2d6 , turkish population , genotyping , allele , allele frequency , genetics , biology , population , cytochrome p450 , polymorphism (computer science) , genotype , microbiology and biotechnology , gene , enzyme , medicine , biochemistry , environmental health
Background and Objectives The genetically polymorphic cytochrome P450 enzymes 2C19 (CYP2C19) 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 (m1), 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 *1×2, *2×2 , or *4×2 (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. Clinical Pharmacology & Therapeutics (1999) 66 , 185–192; doi: 10.1053/cp.1999.v66.100072001