Liu Liang, Yang Lin, Zhang Yan-Chao, Ai Xiao-Fei, Wang Jian-Xiang, Xiao Zhi-Jian
Institute of Hematology & Blood Diseases Hospital, Chinese Academe of Medical Sciences & Peking Union Medical College, State Key Laboratory of Experimental Hematology, Tianjin 300020, China.
Zhonghua Yi Xue Za Zhi. 2009 Oct 20;89(38):2675-81.
To survey the frequencies and characteristics of polymorphism of seven genes coding drug-metabolizing enzymes in a Han Chinese population.
Genomic DNA was extracted from peripheral blood in 1382 unrelated Han Chinese volunteers. Genotypes of CYP450, NQO1, MPO, MTHFR, NAT2, TPMT3B(G460A) and TPMT3C(A719G) were analyzed by PCR-RFLP. GSTM1 and GSTT1 genotypes were detected by multiple PCR and TPMT*2(G238C) genotypes by allele-specific PCR.
The allele frequencies of wild-type, heterozygosity and homozygosity were 99.8%, 0.2% and 0 in CYP3A41B genotypes, 8.4%, 34.3% and 57.3% in CYP3A53 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 TPMT3C(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 NAT24/*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 NAT24, 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 TPMT2(G238C) genotypes and TPMT3B(G460A). The variant alleles of TPMT2(G238C) and TPMT3B(G460A) were not found in 1382 Han Chinese subjects.
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.
调查汉族人群中7种编码药物代谢酶的基因多态性的频率及特征。
从1382名无血缘关系的汉族志愿者外周血中提取基因组DNA。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析CYP450、NQO1、MPO、MTHFR、NAT2、TPMT3B（G460A）和TPMT3C（A719G）的基因型。采用多重PCR检测GSTM1和GSTT1基因型，采用等位基因特异性PCR检测TPMT*2（G238C）基因型。
CYP3A41B基因型中野生型、杂合子和纯合子的等位基因频率分别为99.8%、0.2%和0；CYP3A53基因型中分别为8.4%、34.3%和57.3%；NQO1（C609T）基因型中分别为28.7%、49.7%和21.6%；MPO（G463A）基因型中分别为75.0%、23.2%和1.8%；MTHFR（C677T）基因型中分别为25.9%、44.9%和29.2%；MTHFR（A1298C）基因型中分别为67.3%、30.4%和2.3%；TPMT3C（A719G）基因型中分别为96.8%、3.2%和0。GSTM1中现有基因型和缺失基因型的频率分别为36.1%和63.9%，GSTT1中分别为54.4%和45.6%。NAT24/*4、*4/*5、*4/*6、*4/*7、*5/*5、*5/*6、*5/*7、6/6、6/7和7/7基因型的频率分别为34.5%、4.3%、24.3%、18.2%、0.1%、1.8%、1.5%、5.0%、7.6%和2.6%。NAT2特异性等位基因4、5、6和7的频率分别为57.9%、3.9%、21.8%和16.3%。NAT2快速乙酰化者和慢乙酰化者的基因表型频率分别为81.4%和18.6%。TPMT2（G238C）基因型和TPMT3B（G460A）的野生型等位基因频率均为100%。在1382名汉族受试者中未发现TPMT2（G238C）和TPMT3B（G460A）的变异等位基因。
汉族人群与高加索人群之间，以及汉族人群与黑种人之间，药物代谢酶基因多态性的分布和频率存在显著差异，而在汉族人群与亚洲其他黄种人之间仅观察到一些异质性。
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