Genotyping of the polymorphic drug metabolizing enzymes cytochrome P450 2D6 and 1A1, and N-acetyltransferase 2 in a Russian sample

untersucht. Die Häufigkeit der CYP1A1 Allele mit hoher Aktivität, CYP1A1*2A und Populationen. Abstract The basic principle of drug and xenobiotic metabolism in the body is to make them more water soluble and thus more readily excreted in the urine. Genetic polymorphisms of phases I and II xenobiotic transformation reactions are known to contribute considerably to interindividual variations in the metabolism of numerous drugs and xenobiotics and to associate with altered risk of adverse drug reactions and some cancers. The frequency of functionally important mutations and alleles of genes coding for xenobiotic metabolizing enzymes shows a wide ethnic variation. However, little is known of the frequency distribution of the major allelic variants in the Russian population. In this study we investigated 325 individuals of Russian origin, who were healthy volunteers or patients without malignant diseases. Our study included the complete investigation of two enzymes of phase I, CYP1A1 and CYP2D6, and one phase II enzyme, NAT2, using PCR-RFLP genotyping and LightCycler method. The frequencies of the CYP1A1 high-activity alleles, CYP1A1*2A and CYP1A1*2B, were 4. of alleles, respectively. We did not find the m3 mutation, which has only been detected in Africans up to now. 5.9% (3.5%-9.2%) of all subjects were CYP2D6 poor metabolizers, whereas 3.4% (1.7%-6.3%) were identified as ultra-rapid metabolizers (CYP2D6*1x1/*1). Genotyping eight different single nucleotide polymorphisms in the NAT2 gene provided a genotype associated with slow acetylation in 59.7% (54.1%-65.1%) of individuals, 34.7% (29.6%-40.2%) of participants carried at least one allele encoding rapid acetylation, and 5.6% (3.3%-8.6%) were homozygous for the rapid-acetylation allele (wild-type allele *4 or mutant allele *12A). The overview of allele distribution of the important drug and xenobiotic metabolizing enzymes among Russians shows that the allele frequency is similar to that of other Caucasians. Therefore it may be expected that drug side effects and efficacy problems due to an individual's genetic background are similar compared to those in other European populations.