中文摘要：

目的了解汉族人群7种主要药物代谢酶基因14个多态性位点基因型的分布频率及其特征。方法收集1382名汉族人外周血样品，常规提取基因组DNA。用PCR-限制性内切酶片段长度多态性方法检测细胞色素P450酶（CYP450）的CYP3A4＊1B、CYP3A5＊3、苯醌氧化还原酶1（NQ01）的C609T（NQO1C609T）、髓过氧化物酶（MPO）的G463A（MPOG463A）、5，10-亚甲基四氢叶酸还原酶（MTHFR）的C677T（MTHFRC677T）、A1298C（MTHFRA1298C）、N-乙酰基转移酶2（NAT2）的NAT2＊5AC481T、NAT2＊6AG590A、NAT2＊7AC857A和巯基嘌呤-S-甲基转移酶（TPMT）的TPMT＊3BG460A、TPMT＊3C4719G多态性位点基因型，用多重PCR方法检测谷胱甘肽硫转移酶（GST）的GSTM1、GSTT1基因型，用等位基因特异性PCR（AS—PCR）检测TPMT＊2G238C基因型。结果野生、杂合变异和纯合变异基因型频率CYP3A4＊1B分别为99．8％、0．2％和0，CYP3A5＊3为8．4％、34．3％和57．3％；NQO1C609T为28．7％、49．7％和21．6％；MPOC463A为75．0％、23．2％和1．8％；MTHFRC677T为25．9％、44．9％和29．2％，MTHFRA1298C为67．3％、30．4％和2．3％；TPMT＊3CA719G为96．8％、3．2％和0。表达型和缺失型基因型频率GSTM1分别为36．1％和63．9％，GSTT1分别为54．4％和45．6％。NAT2＊4／＊4、＊4／＊5、＊4／＊6、＊4／＊7、＊5／＊5、＊5／＊6、＊5／＊7、＊6／＊6、＊6／＊7和＊7／＊7基因型频率分别为34．5％、4．3％、24．3％、18．2％、0．1％、1．8％、1．5％、5．0％、7．6％和2．6％，NAT2＊4、＊5、＊6和＊7等位基因频率分别为57．9％、3．9％、21．8％和16．3％，快乙酰化和慢乙酰化基因表型频率分别为81．4％和18．6％。TPMT＊2G238C和TPMT＊3BG460A野生基因型频率均为100％。结论药物代谢酶基因常见的遗传多态性在中国汉族人群中的分布及其频率与白种人和黑种人存在明显差异，与亚洲其他黄种?

英文摘要：

Objective To survery the frequencies and characterstics 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 ＊ 3BC460A and TPMT ＊ 3CA719G were analyzed by PCR-RFLP. GSTM1 and GSTF1 genotypes were detected by multiple PCR and TPMT ＊ 2G238C 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 NQOlc609T genotypes, 75.0% , 23.2% and 1.8% in MPOC463A genotypes, 25.9% , 44.9% and 29.2% in MTHFRC677T genotypes, 67.3%, 30.4% and 2.3% in MTHFRA1298C genotypes, and 96.8% 3.2% and 0 in TPMT ＊ 3CA719C genotypes, respectively. The frequencies of present and null genotypes were 36.1% and 63.9% in GSTM1, 54.4% and 45.6% in GSTrl 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 frequencie of wild type were 100% in both TPMT ＊ 2G238C genotypes and TPMT ＊ 3BC460A. The variant alleles of TPMT ＊ 2G138C and TPMT ＊ 3BG460A were not found in 1582 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 Melanoderms while only some heterogeneity has been observed between Han Chinese population and other Xanthode