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Analysis Of SNPS Genetic Polymorphisms In CYP3A4and CYP2D6in Chinese Han Population

Posted on:2014-07-07Degree:MasterType:Thesis
Country:ChinaCandidate:D YangFull Text:PDF
GTID:2254330425954578Subject:Forensic medicine
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Backgroud:In forensic science, ambiguous drug-related deaths can bedifficult to interpret due to the inter-individual variability in the response todrugs. Some causes include environmental and physiological factors anddrug–drug interactions. however, the The most critical factors is inheritedas a result of polymorphisms in drug metabolising enzymes (DMEs).Cytochrome P450(CYP), one of the most important DMEs, has manygenetic variations, leading to inter-individual differences in the response todrugs, which may result in adverse side effects。drug-metabolizing enzymesinvolved in the metabolism mainly by CYP2C9, CYP2C19, CYP2D6andCYP3A4,etc. CYP3A4accounted for about30%of the total content ofhuman liver microsomal CYP enzymes, but the metabolism of more than50%of the drug in clinical; CYP2D6as the only activity in vivo of CYP2Dsubfamily enzyme accounted for only P450liver total protein of1%to2%,but it Participated about30%of drug metabolism in clinical, they areimportant drug-metabolizing enzymes CYP enzymes.0bjective: To get the data of genetic polymorphisms in the ChineseHan population, through screening and detecting drug-metabolizingenzyme CYP2D6and CYP3A4SNPs, And through analysis date, observed study population SNPs polymorphism and compared with the Caucasianpopulation data, analysis SNP in the Chinese Han population.Method: We screened11SNPs in these2CYP genes. Genomic DNAwas prepared from192blood samples obtained from individuals ofChinese Han origin. the polymorphisms were analysed by allele-specificprimer extension followed by SNPstream Analysis System. all theanalysed SNPs were polymorphic.Results: All11of the analysed SNPs were polymorphic (MAF>0.01).Of these11SNPs,8(RS28624811, RS28670611, RS9623531, RS5758589,RS3735451, RS2246709, RS2404955, RS4646440) had an allele frequencythat was significantly different between this Chinese Han population andCaucasians (P <0.01).Conclusions: With Large sample size in this study,CYP2D6andCYP3A4gene polymorphisms in Chinese Han population reveals Hanpopulation in some of which sites may inherit a specific geneticinformation, that could lead to different drug metabolism rates. these datefor Han population related drugs Metabolize would have better responses,And for the identification of the cause of death ambiguous drug-relateddeath offered a new way.
Keywords/Search Tags:SNP, CYP2D6, CYP3A4, introns
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