Global pharmacogenetics: genetic substructure of Eurasian populations and its effect on variants of drug-metabolizing enzymes.
AIMS: To study the frequency distribution of cytochrome P450 (CYP) functional genetic variants in five Eurasian populations from the territory of Siberia in Russia. MATERIALS & METHODS: Unrelated healthy Tuvinians, Buryats, Altaians, Yakuts and Russians (n = 87-88) were genotyped for CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, CYP3A5*3 and CYP3A5*6. Standard pairwise genetic distances, locus-specific and global Fst statistics were calculated. RESULTS: CYP allele and genotype frequencies demonstrated significant variability. Overall, the degree of between-population variance displayed by CYP SNPs was lower than that recorded from neutral short tandem repeats and Alu-insertion polymorphism, indicating evolutionary conservation of CYP polymorphisms. CYP-based genetic distances were well correlated with the geographic distances across populations (r = 0.822, p = 0.008). CONCLUSIONS: Although the tested variants were present in the neighboring, yet secluded, populations at the expected range of frequencies, the observed frequencies were significantly variable across Eurasian populations, indicating potential relevance to clinical decision making.
Makeeva, O; Stepanov, V; Puzyrev, V; Goldstein, DB; Grossman, I
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