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  • Title: [Polymorphisms of drug-metabolizing enzymes genes in a Han Chinese population].
    Author: Liu L, Yang L, Zhang YC, Ai XF, Wang JX, Xiao ZJ.
    Journal: Zhonghua Yi Xue Za Zhi; 2009 Oct 20; 89(38):2675-81. PubMed ID: 20137266.
    Abstract:
    OBJECTIVE: To survey the frequencies and characteristics of polymorphism of seven genes coding drug-metabolizing enzymes in a Han Chinese population. METHODS: Genomic DNA was extracted from peripheral blood in 1382 unrelated Han Chinese volunteers. Genotypes of CYP450, NQO1, MPO, MTHFR, NAT2, TPMT*3B(G460A) and TPMT*3C(A719G) were analyzed by PCR-RFLP. GSTM1 and GSTT1 genotypes were detected by multiple PCR and TPMT*2(G238C) genotypes by allele-specific PCR. RESULTS: The allele frequencies of wild-type, heterozygosity and homozygosity were 99.8%, 0.2% and 0 in CYP3A4*1B genotypes, 8.4%, 34.3% and 57.3% in CYP3A5*3 genotypes, 28.7%, 49.7% and 21.6% in NQO1(C609T) genotypes, 75.0%, 23.2% and 1.8% in MPO(G463A) genotypes, 25.9%, 44.9% and 29.2% in MTHFR(C677T) genotypes, 67.3%, 30.4% and 2.3% in MTHFR(A1298C) genotypes, and 96.8% 3.2% and 0 in TPMT*3C(A719G) genotypes, respectively. The frequencies of present and null genotypes were 36.1% and 63.9% in GSTM1, 54.4% and 45.6% in GSTT1 respectively. The frequencies of NAT2*4/*4, *4/*5, *4/*6, *4/*7, *5/*5, *5/*6, *5/*7, *6/*6, *6/*7 and *7/*7 genotypes were 34.5%, 4.3%, 24.3%, 18.2%, 0.1%, 1.8%, 1.5%, 5.0%, 7.6% and 2.6% respectively. The frequencies of specific NAT2 alleles were 57.9%, 3.9%, 21.8% and 16.3% for NAT2*4, *5, *6 and *7 respectively. The frequencies of genophenotypes were 81.4% and 18.6% in NAT2 fast acetylator and low acetylator respectively. The allele frequency of wild type were 100% in both TPMT*2(G238C) genotypes and TPMT*3B(G460A). The variant alleles of TPMT*2(G238C) and TPMT*3B(G460A) were not found in 1382 Han Chinese subjects. CONCLUSION: Significant differences in the distributions and frequencies in genetic polymorphisms of drug-metabolizing enzymes are identified between Han Chinese population and Caucasians, as well between Han Chinese population and Melanoderma while only some heterogeneity has been observed between Han Chinese population and other Xanthoderms in Asia.
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