中国人CYP3A4的新突变。
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谢国平，林云云，程春林，赖明明，林淑梅，西志平，黄景德
中国人CYP3A4的新突变。
《药物代谢处置》2001 Mar;29(3):268-73。
- PubMed ID
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11181494 (PubMed视图］
- 摘要
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人类细胞色素P450 3A4是肝脏和胃肠道中的主要P450酶。它在多种药物、一些内源性类固醇和有害环境污染物的代谢中起着重要作用。CYP3A4表现出显著的个体间活性差异，高达20倍。为了研究CYP3A4基因多态性是否可以部分解释个体间CYP3A4水平的变异，我们采用聚合酶链反应(PCR)-单链构象多态性分析方法分析了102例中国人的DNA样本，发现CYP3A4编码序列和启动子区出现了新的点突变。使用PCR直接测序方法建立完整的内含子序列的CYP3A4白细胞,完整的基因组序列从外显子1到13 CYP3A4的决心和数据库(加入没有发表在基因库。AF209389)。据此设计cyp3a4特异性引物。通过pcr -单链构象多态性和限制性片段长度多态性筛选，发现3个新突变;两个是点突变，一个是插入。第一个变异等位基因(CYP3A4*4)， Ile118Val变异，在102名中国受试者中有3名被发现。 The next allele (CYP3A4*5), which causes a Pro218Arg amino acid change, was found in 2 of 102 subjects. We found an insertion in A(17776), designated as CYP3A4*6, which causes frame shift and an early stop codon in exon 9, in one heterozygous subject. We also investigated the CYP3A4 activity in these mutant subjects by measuring the morning spot urinary 6beta-hydroxycortisol to free cortisol ratio with the enzyme-linked immunosorbent assay method. When compared with healthy Chinese population data, the 6beta-hydroxycortisol to free cortisol ratio data suggested that these alleles (CYP3A4*4, CYP3A4*5, and CYP3A4*6) may decrease the CYP3A4 activity. Incidences of these mutations in Chinese subjects are rare. The prevalence of these point mutations in other ethnic groups and its effect on the metabolic activity of CYP3A4 remain to be further evaluated.