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The Study On The CYP4502E1 Gene Polymorphism And Its Significance In Forensic Medicine And Population Genetics

Posted on:2006-12-05Degree:MasterType:Thesis
Country:ChinaCandidate:Z F LiuFull Text:PDF
GTID:2166360152496954Subject:Forensic medicine
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IntroductionCytochrome P450s are series of super family genes that composition and function are very similar, which have an absorb peak at 450nm when binding with CO. In human CYP super gene family, there are three major gene family CYP4501,CYP4502 and CYP4503 which take part in the outward source bio transformation. It has been found that at least 19 kinds of CYP450 that take part in the drug metabolism, lots of study have attested that it varies in drug metabolism between people. Perhaps it was made by genetics and surroundings. CYP450 is regulated by genetic genes. Once the gene mutates, the CYP450 enzyme that coded and the drug metabolism then will change. So the CYP450 polymorphisms are the basis of the ethic and individual difference in drug mata-bilism. It has been known that there are CYP4501A1, CYP4501A2, CYP4502A6,CYP4502C,CYP4502D6,CYP4502El and CYP4503A4 et al that have genetic polymorphisms. The most study on CYP4502E1.CYP4502E1 is bimethyl nitrosamine D - methyl enzyme, which major take part in activating the low molecular carcinomatous such as benzene, tetrachlo-ride et al. it also concerned with the alcohol oxidation and reduce free radical. Most of CYP4502E1 is in liver, elsewhere such as oesophagus and lung also has CYP4502E1 expressed. Although CYP4502E1 is abduct by surrounding factors such as alcohol. It has obviously difference in individuals whether before or after, which means its express is determined by genetics. Lots of study have attested that CYP450 gene polymorphism are association with its metabolic activity.CYP4502E1 gene is locate in chromosome 10, It has 9 exons and 8 in-trons. Up to the date there are 5 restrict fragment length polymorphism sites, TaqI,DraI,RsaI,MspI and 5'RsaI/PstI. The 5'RsaI/PstI and Dral have influence on CYP4502E1 expression. Dral locus is on intron 6, it has two alleles: there lies a Dral locus in allele D, whereas the allele C has mutation (T—?A) in 7668 bp then the locus disappear, cl gene has Rsal locus but not Pstl locus,on the contrary, C2 allele has Pstl locus but not Rsal locus. We use PCR - RFLP technology in this study, investigating the polymorphisms in Chinese han and Tibertian population of this two loci, offering the basic data to their use in forensic medicine. As they vary in ethic distribution, So they are also very important in studying the people migrate.Material and methodsOrdering the primer by articles, we use PCR method to amplify the Rsal/ Pstl locus and Dral locus on the cytochrome, and use Rsal/PstI and Dral restriction endonucleases digest them, by PAGE followed sliver stain. We genotype the genes of 162 Chinese han and 119 Tibetan individuals.ResultsIn 162 Chinese han individuals, we found two alleles and three genotypes: homozygote cl/cl was 107 individuals, its frequency was 0.6542; heterozygote cl/c2 was 52 individuals, its frequency was 0. 3210, homozygote c2/c2 was 4 individuals, its frequency was 0.0248. allele cl frequency was 0. 8147, alleles c2 frequency was 0. 1853. we found two genotypes and three alleles, homozygote CC frequency was 13 individuals, its frequency 0.00802; heterozygote CD was 58 individuals, its frequency was 0. 3580;homozygote DD was 91 individuals, its frequency was 0. 5617. alleles C frequency was 0.2592, alleles D frequency was 0.7408. In 119 Tibetan individuals, we found homozygote cl/cl was 65 individuals, its frequency was 0.5462; heterozygote cl/c2 was 50 individuals, its frequency was 0.4202, homozygote c2/c2 was 4 individuals, its frequency was...
Keywords/Search Tags:cytochrome P450, single nucleotide polymorphism, PCR - RFLP, Hans, Tibetan
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