Genetic polymorphism of CYP2D6 in North Indian subjects

Objectives: CYP2D6 polymorphism of clinical relevance occurs with variable frequency in different ethnic groups. Since this polymorphism has not been studied in a North Indian population, the present study was undertaken. Methods: One hundred healthy unrelated North Indian subjects received 30 mg dextromethorphan (DM) orally at bed-time. The amounts of DM and its metabo lite, dextrorphan (DR), excreted in 8 h urine were estimated by high perfor mance liquid chromatography. Metabolic ratio (DM/DR excreted in 8 h) was us ed as an index of the metabolic status of an individual. Results: The analysis of the data by frequency distribution histogram, prob it and NTV plots demonstrated bimodal distribution of the North Indian subj ects with respect to hepatic CYP2D6. Out of 100 subjects, 97 were extensive metabolizers (EMs), whereas three were poor metabolizers (PMs). EMs and PM s excreted 29.82 and 2.67 mu mol DR (mean value) and 2.59 and 8.82 mu mol D M (mean value) in 8 h, respectively. MR and log MR was 197- and 2.2-fold hi gher in PMs versus EMs. The antimode value of zero was determined by visual observation in frequency distribution histogram and inflection point in pr obit plot. Conclusion: From this study, it can be concluded that the PM phenotype of C YP2D6 occurs with a frequency of 3% (95% confidence interval of 0.33%-6.33% ) in North Indians.