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The effect of the CYP2C19 genotype on the hydroxylation index of omeprazole in South Indians

  • Pharmacogenetics
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Abstract

To investigate the relationship between CYP2C19 genotypes and the hydroxylation index (HI) of omeprazole in the South Indian population. Healthy unrelated South Indian subjects (n=300) were separated into three groups based on their CYP2C19 genotypes. They were administered a single oral dose of 20 mg omeprazole, and venous blood was collected 3 h later. Plasma was assayed using reversed-phase high-performance liquid chromatography, and the omeprazole HI was calculated. The means of HIs in individuals with CYP2C19*1/*1 (n=124), *1/*2 (n=129) and *2/*2,*2/*3 (n=47) were 2.4, 5.3 and 22.5, respectively, and were found to be significantly different between any two groups (P<0.0001). A good correlation was established between CYP2C19 genotype and omeprazole HI (r=0.54, 95% CI 0.45–0.62; P<0.0001). Of the 300 subjects, 42 (14.0%; 95% CI 10.1–17.9) were phenotypic poor metabolizers (PMs), but only 33 of them had two mutant alleles and the remaining 9 PMs had at least one wild-type allele. Among the 258 extensive metabolizers, 14 had two mutant alleles. The prevalence of PMs in the South Indian population was 14.0%, which is similar to that in North Indians and Orientals but significantly higher than in Caucasians and Africans. A genotype–phenotype relationship was established between the CYP2C19 genotype and HI of omeprazole, but 7.7% of subjects deviated from expected genotype–phenotype associations. This could be due to an additional mutation, either in the exons/introns or in the 5′-regulatory region of the CYP2C19 gene.

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Acknowledgements

This research project was funded by the Indian Council of Medical Research, New Delhi, India and INSERM, Paris, France (ICMR Ref. No. 50/6/2000-BMS dated 11/12/2001). We thank Dr. Kjell Andersson, AstraZeneca, Sweden, who very kindly provided us a gift of the pure powder of 5-hydroxy omeprazole and Torrent Chemicals, Ahmedabad, India for omeprazole. We thank Mr. S. Subramaniam, Technical Officer, Division of Population Science, Modelling and Bio-informatics, Vector Control Research Centre, Pondicherry, India, for his help with statistical analysis. We are grateful to Mr. R. Balakrishnan, Mr. S. Rajan and Ms. S. Mala, for technical assistance. There are no conflicts of interest regarding financial or other relationships.

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Authors and Affiliations

  1. Department of Pharmacology, Pharmacogenomics Laboratory, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605 006, India

    J Rosemary, C Adithan, N Padmaja & C H Shashindran

  2. INSERM U-458, Hopital Robert Debre, 48 Boulevard Serurier, 75019, Paris, France

    N Gerard & R Krishnamoorthy

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  1. J Rosemary
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  2. C Adithan
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Correspondence to C Adithan.

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Rosemary, J., Adithan, C., Padmaja, N. et al. The effect of the CYP2C19 genotype on the hydroxylation index of omeprazole in South Indians. Eur J Clin Pharmacol 61, 19–23 (2005). https://doi.org/10.1007/s00228-004-0833-1

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  • DOI: https://doi.org/10.1007/s00228-004-0833-1

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