Global pharmacogenetics: genetic substructure of Eurasian populations and its effect on variants of drug-metabolizing enzymes.
OBJECTIVE
To study the frequency distribution of cytochrome P450 (CYP) functional genetic variants in five Eurasian populations from the territory of Siberia in Russia.


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
Oksana
O
Tomsk Research Institute of Medical Genetics, The Russian Academy of Medical Sciences, 10 Nab. Ushaiky, Tomsk, 634050 Russia. oksana.makeeva@medgenetics.ru
Stepanov
Vadim
V
Puzyrev
Valery
V
Goldstein
David B
DB
Grossman
Iris
I
D000483:Alleles; D044466:Asian People / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D012800:Siberia; D044465:White People / Q000235:genetics*
D004364:Pharmaceutical Preparations; D004247:DNA; D003577:Cytochrome P-450 Enzyme System