NAT2和CYP2E1基因多态性及其代谢表型在中国汉族儿童中的分布

目的：N-乙酰基转移酶-2（NAT2）和细胞色素氧化酶P450 2EI（CYP2E1）在药物的代谢过程中起重要的作用。该研究旨在了解NAT2、CYP2E1的基因多态性及其代谢表型在中国汉族儿童中的分布，为实现药物的个体化治疗提供参考依据。方法：应用聚合酶链式反应并测序的方法检测341例中国汉族儿童（年龄0~14岁，男211例，女130例）NAT2、CYP2E1的重要SNPs基因型，并判定其代谢表型。结果：在中国汉族儿童中，NAT2的7个SNPs（rs1801279、rs1041983、rs1801280、rs1799929、rs1799930、rs1208、rs179993）基因型均以野生型为主；NAT2代谢表型以快代谢型的频率最高（61.3%），其次是中间/慢代谢型（34.1%）。CYP2E1的4个重要SNPs基因型（rs2031920、rs3813867、rs6413432、rs72559720）被命名为：CYP2E1*5、*6、*2，均以野生型为主，野生型频率分别为：61.3%、60.1%、99.4%；由于CYP2E1基因型和代谢表型的关系还未明确，未对其进行代谢表型分型。结论：NAT2基因在中国汉族儿童中的分布以野生型/快代谢型为主，CYP2E1基因以野生型为主，基因型/代谢表型在中国汉族儿童中的多态性分布为药物的个体化治疗提供参考依据。

Genotype and phenotype polymorphisms of NAT2 and CYP2E1 in the Han Chinese pediatric population

Objective N-acetyltransferase 2(NAT2) and cytochrome P450 2EI(CYP2E1) play a crucial role in the drug metabolic process.The aim of this study was to understand the genotype and phenotype polymorphisms of NAT2 and CYP2E1 in the Han Chinese pediatric population in order to provide a theoretical basis for individualized drug treatment.Methods A total of 341(211 males and 130 females) randomly sampled Han Chinese children,aged from 2 months to 14 years,were enrolled in this study.Genotyping was carried out by PCR method,and metabolic phenotypes were identified.Results In this study population,wild genotype was found as a major genotype in seven SNPs of NAT2,rs1801279,rs1041983,rs1801280,rs1799929,rs1799930,rs1208 and rs1799931.The frequency of NAT2 fast metabolism was highest(61.3%),followed by middle to slow metabolism(34.1%).Wild genotype also predominated in the four SNPs of CYP2E1(rs2031920,rs3813867,rs6413432 and rs72559720) named as CYP2E1*5,*6 and *2,with a frequency of 61.3%,60.1% and 99.4% respectively.As the relationship between CYP2E1 genotype and phenotype was unknown,phenotyping of CYP2E1 was not done.Conclusions The important SNPs of NAT2 and CYP2E1 are predominantly wild genotype in the Han Chinese pediatric population.Fast metabolic phenotype predominates in important SNPs of NAT2.