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Genotype–phenotype correlation of cytochrome P450 2C9 polymorphism in Indian National Capital Region

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Abstract

Identification of polymorphism of cytochrome P450 2C9 (CYP2C9) enzymes in different ethnic populations is important to understand the differences in clinical responses to drugs. This study determines the CYP2C9 genetic polymorphism in Indian National Capital Region and correlates the phenotype–genotype. Losartan (25 mg) was administered to 107 volunteers to assess CYP2C9 activity, and, on the basis of results, volunteers were categorized as rapid and poor metabolizers. Molecular typing of CYP2C9*1 (wild type), CYP2C9*2, and CYP2C9*3 (the most common variant) was carried out by single-base primer extension technology for 37 subjects, of which 9 were poor metabolizers, and 28 were rapid metabolizers. 14.28 % of the studied population was identified as poor metabolizer for the category of drugs metabolized by CYP2C9. Significant difference was observed between the mean ratio (drug/metabolite) of poor (11.38 ± 5.88) and rapid (1.18 ± 1.11) drug metabolizers. The study suggests that phenotyping of CYP2C9 is desirable before enrollment of subjects for clinical trials or for deciding drug dose regimen as 14.28 % of study population was found to be poor metabolizer for the category of drugs metabolized by CYP2C9. This study establishes phenotype–genotype correlation, and proposes to use genotyping or phenotyping to evaluate the status of drug metabolizing capacity of CYP2C9 as a primary screening procedure before enrolling subjects in clinical trials or in clinical practice.

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Acknowledgments

Authors thank all the study participants. TCGA (Tata Center for Genomic Application) is thanked for the facility to carry out genotyping procedure. The Department of Biochemistry acknowledges UGC for SAP (DRS-1), and DBT for the Bioinformatics Infrastructure Facility at JH.

Conflict of interest

The authors declare that there is no conflict of interest. SA is responsible for the overall supervision of the study and made critical contributions at all stages and finalized the paper for submission. EV, a PhD student under the supervision of SA, executed the study. NA provided approval for conducting clinical trials in Ranbaxy Laboratories Limited, MT co-supervised the work, and VS is responsible for all statistical analysis.

Protection of human subjects

The study protocol and the corresponding informed consent form (ICF) were reviewed by the Institutional Review Board and the procedures were in accordance with the Helsinki Declaration of 1975, as revised in 2000.

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Authors and Affiliations

  1. Department of Biochemistry, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi, 110062, India

    Ekta Varshney & Shakir Ali

  2. Ranbaxy Clinical Pharmacology Unit, Ranbaxy Laboratories Limited, Gurgaon, India

    Ekta Varshney, Nilanjan Saha, Monika Tandon & Vikesh Shrivastava

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  1. Ekta Varshney
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  2. Nilanjan Saha
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Correspondence to Shakir Ali.

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Varshney, E., Saha, N., Tandon, M. et al. Genotype–phenotype correlation of cytochrome P450 2C9 polymorphism in Indian National Capital Region. Eur J Drug Metab Pharmacokinet 38, 275–282 (2013). https://doi.org/10.1007/s13318-013-0124-2

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  • DOI: https://doi.org/10.1007/s13318-013-0124-2

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