利用右美沙芬区分细胞色素P4502D6纯合子与杂合子快代谢者
DISTINGUISHING CYP2D6 HOMOZYGOUS AND HETEROZYGOUS EXTENSIVE METABOLIZERS BY DEXTROMETHORPHAN PHENOTYPING
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摘要: 本研究目的是建立准确的细胞色素P450 2D6(CYP2D6)的右美沙芬表型测定法,以发现CYP2D6纯合子与杂合子快代谢者的表型差异。通过提高右美沙芬的检测灵敏度(1ng·mL-1)而建立的HPLC分析法,对已知基因型的3组共168位受试者进行表型测定。结果发现不仅快代谢者与慢代谢者在代谢率上有很大差异,纯合子快代谢者与杂合子快代谢者之间在代谢率上也有差异。提示CYP2D6基因表达时,基因拷贝数起一定的作用。Abstract: A more sensitive procedure was developed to phenotype cytochrome P450 2D6 metabolism by a less toxic probe drug—dextromethorphan. The sensitivity of the determination of dextromethorphan in urine samples was up to 1 ng·ml-1. This method was employed to phenotype three groups of subjects. The results showed that there was a difference between extensive metabolizers which were genotyped as homozygotes and heterozygotes. Although the difference was not as big as the difference with poor metabolizers which were genotyped as homozygous mutants. It suggests that “gene copy” is a true factor in the expression of CYP2D6 genes.
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