CAJ | 학술논문

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(NQO1)的C609T(NQO1_(C609T))、髓过氧化物酶(MPO)的G463A(MPO_(G463A))、5,10-亚甲基四氢叶酸还原酶(MTHFR)的C677T(MTHFR_(C677T))、A1298C(MTHFR_(A1298C))、N-乙酰基转移酶2(NAT2)的NAT2* 5A_(C481T)、NAT2 * 6A_(G590A)、NAT2 * 7A_(G857A)和巯基嘌呤-S-甲基转移酶(TPMT)的TPMT * 3B_(G460A)、TPMT * 3C_(A719G)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 * 2_(G238C)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%;NQO1_(C609T)为28.7%、49.7%和21.6%;MPO_(G463)A为75.0%、23.2%和1.8%;MTHFR_(C677T)为25.9%、44.9%和29.2%,MTHFR_(A1298C)为67.3%、30.4%和2.3%;TPMT * 3C_(A719G)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*2_(G238C)和TPMT*3B_(G460A)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,与亚洲其他黄种人也存在一定的差异.
목적 료해한족인군7충주요약물대사매기인14개다태성위점기인형적분포빈솔급기특정.방법 수집1382명한족인외주혈양품,상규제취기인조DNA.용PCR-한제성내절매편단장도다태성방법검측세포색소P450매(CYP450)적CYP3A4 * 1B、CYP3A5 * 3、분곤양화환원매1(NQO1)적C609T(NQO1_(C609T))、수과양화물매(MPO)적G463A(MPO_(G463A))、5,10-아갑기사경협산환원매(MTHFR)적C677T(MTHFR_(C677T))、A1298C(MTHFR_(A1298C))、N-을선기전이매2(NAT2)적NAT2* 5A_(C481T)、NAT2 * 6A_(G590A)、NAT2 * 7A_(G857A)화구기표령-S-갑기전이매(TPMT)적TPMT * 3B_(G460A)、TPMT * 3C_(A719G)다태성위점기인형,용다중PCR방법검측곡광감태류전이매(GST)적GSTM1、GSTT1기인형,용등위기인특이성PCR(AS-PCR)검측,TPMT * 2_(G238C)기인형.결과 야생、잡합변이화순합변이기인형빈솔CYP3A4 * 1B분별위99.8%、0.2%화0,CYP3A5 * 3위8.4%、34.3%화57.3%;NQO1_(C609T)위28.7%、49.7%화21.6%;MPO_(G463)A위75.0%、23.2%화1.8%;MTHFR_(C677T)위25.9%、44.9%화29.2%,MTHFR_(A1298C)위67.3%、30.4%화2.3%;TPMT * 3C_(A719G)위96.8%、3.2%화0.표체형화결실형기인형빈솔GSTM1분별위36.1%화63.9%,GSTT1분별위54.4%화45.6%.NAT2*4/*4、*4/*5、*4/*6、*4/*7、*5/*5、*5/*6、*5/*7、*6/*6、*6/*7화*7/*7기인형빈솔분별위34.5%、4.3%、24.3%、18.2%、0.1%、1.8%、1.5%、5.0%、7.6%화2.6%,NAT2*4、*5、*6화*7등위기인빈솔분별위57.9%、3.9%、21.8%화16.3%,쾌을선화화만을선화기인표형빈솔분별위81.4%화18.6%.TPMT*2_(G238C)화TPMT*3B_(G460A)야생기인형빈솔균위100%.결론 약물대사매기인상견적유전다태성재중국한족인군중적분포급기빈솔여백충인화흑충인존재명현차이,여아주기타황충인야존재일정적차이.
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*3B_(C460A) 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*1 B 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%and63.9%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 spocific 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 beth 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 difierences 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 Xanthoderms in Asia.