Research On Function And Oligonucleotide Microarray Detection Of Cytochrome P450 Hot Mutation

As a significant role in endo- and exo-genous compound metabolism, the Cytochrome P450 takes part in metabolic activation of variant drugs, precarcinogens, prepoisons and biomodifier and deletion of about 60% of all drugs. In the CYP450 system, the function and qualities of CYP450 1-3 family are more attractive as the studies on them proceeded widespreadly.The first part of this paper was specialized in genotyping of CYP2D6 SNPs C188T and G4268C, making up wild type, heterozygosis mutant and homozygosis mutant SNPs of 240 health volunteers to analyze genotyping results. Moreover, the explaination and discussion of the relationship between the results of CYP2D6 genotyping and value of pharmacokinetics parameters was carried out. The genotyping result indicated that the incidence frequency of allele CYP2D6ch was rather high, as the homozygosis mutant percentage of C188T and G4268C sites got to 53% and 54% respectively, which was in well accordance with those results reported outside. Associating with pharmacokinetics test (metoprolol tartrate as the probe drug), we verificated the association of genetic polymorphisms and metabolic phenotypes involving utilization of direct sequencing results. Then the relevant conclusion was able to bring out for personalized medicine by initial clarification of the relation between genotype and function pattern of CYP2D6 in Chinese population.The pharmacokinetics test was carried on by choosing 40 volunteers in the same population as 4 groups according genotyping results, to detect the concentration of prodrug and α-hydroxylmeteprolol, one of its metabolites by use of HPLC. This pharmacokinetics research indicated that, there is no significant difference in pharmacokinetics parameter between the 1st group (CYP2D6*2W*10W) and the 2nd group (CYP2D6*2H*10W/*2M*10W) (P>0.05). Otherwise, the 3rd group (CYP2D6*2M*10H) compared with the 1st group, in the blood, t_1/2 and AUC0-32 of meteprolol increased by 33.8% and 90.3% respectively, while there was a growth of t_1/2 by 47.3% and decrease of AUC0-32 and C_max of a-hydroxylmeteprolol by 40.8% and 43.9%. On the contrary, the prodrug increased or metabolite decreased in the...