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Genetic polymorphism of CYP2D6 in North Indian subjects
V Lamba1, J K Lamba, J B Dilawari
1Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, UT, India.
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 metabolite, dextrorphan (DR), excreted in 8 h urine were estimated by high performance liquid chromatography. Metabolic ratio (DM/DR excreted in 8 h) was used as an index of the metabolic status of an individual.
Results:
The analysis of the data by frequency distribution histogram, probit and NTV plots demonstrated bimodal distribution of the North Indian subjects with respect to hepatic CYP2D6. Out of 100 subjects, 97 were extensive metabolizers (EMs), whereas three were poor metabolizers (PMs). EMs and PMs excreted 29.82 and 2.67 micromol DR (mean value) and 2.59 and 8.82 micromol DM (mean value) in 8 h, respectively. MR and log MR was 197- and 2.2-fold higher in PMs versus EMs. The antimode value of zero was determined by visual observation in frequency distribution histogram and inflection point in probit plot.
Conclusion:
From this study, it can be concluded that the PM phenotype of CYP2D6 occurs with a frequency of 3% (95% confidence interval of 0.33%-6.33%) in North Indians.