CYP2D6 Genotyping With Gene Chip And Influence Of Genetic Polymorphism On The Pharmacokinetic Interactions Between Tramadol And Metoprolol In A Chinese Population

Cytochrome P450 2D6 (CYP2D6) is an important drug-metabolizing enzyme, which metabolizes nearly 100 drugs. CYP2D6 was first identified as the polymorphic enzyme involved in debrisoquine hydroxylation and sparteine oxidation. Currently more than 70 different alleles have been described. In this study, gene chips are created to evaluate the allelic frequency of CYP2D6 and investigate the influence of genetic polymorphism of CYP2D6 on pharmacokinetic interactions between tramadol and metoprolol in a Chinese population.1. Screening the genetic polymorphism of CYP2D6 in a Chinese population by gene chipsAccording to the distributing feature of the polymorphisms in CYP2D6 gene, specially aimed to C188T and G4268C, the two mutant sites reported to have the potent effects in the drug metabolism of Chinese people, gene chips are created with a set of designed oligonuceotides probes. 312 DNA samples from Chinese healthy volunteers were genotyped and parts of samples were validated by direct sequencing. The results of these two genotyping methods are in concordance which indicates that the gene chips established in this study can be applied to screen the genotypes of CYP2D6 in a Chinese population. The allelic frequencies of CYP2D6 were 8.3% (CYP2D6*2W*10W), 13.5% (CYP2D6*2H*10W), 10.6% (CYP2D6*2M*10W),...