Skip to main content

Advertisement

SpringerLink
Log in

Determination of −3858G→A and −164C→A genetic polymorphisms of CYP1A2 in blood and saliva by rapid allelic discrimination: large difference in the prevalence of the −3858G→A mutation between Caucasians and Asians

  • Short Communication
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Introduction

Two mutations in CYP1A2, −164C→A (allele CYP1A2*F) and −3858G→A (allele CYP1A2*C), affecting the inducibility of the enzyme, have been published. The aim of this study was to develop a high throughput allelic discrimination assay for these mutations in both saliva and blood and to determine their frequency in Caucasians.

Methods

An allelic discrimination assay, based on the fluorogenic 5′-nuclease activity (TaqMan), was developed for the two mutations. Genomic DNA extracted from 17 saliva and 100 blood samples from Caucasians was analysed.

Results and conclusions

For the −164C→A mutation, we found an allelic frequency of 68% in the Caucasian population, comparable with data published for Asians and Caucasians. For the −3858G→A mutation, the allele frequency was only 2% in Caucasians, a much lower value than the ~25% reported in Asians (P<0.001). The presented allelic discrimination allows fast and accurate detection of these two mutations. Genotype calls were 100% identical for DNA from saliva and blood. Saliva is easily accessible and represents an excellent alternative to the traditionally used venous blood for genotyping.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ingelman-Sundberg M (2001) Genetic susceptibility to adverse effects of drugs and environmental toxicants. The role of the CYP family of enzymes. Mutat Res 482:11–19

    Article  CAS  PubMed  Google Scholar 

  2. Boobis AR, Lynch AM, Murray S, de la Torre R, Solans A, Farre M, Segura J, Gooderham NJ, Davies DS (1994) CYP1A2-catalyzed conversion of dietary heterocyclic amines to their proximate carcinogens is their major route of metabolism in humans. Cancer Res 54:89–94

    CAS  PubMed  Google Scholar 

  3. Butler MA, Guengerich FP, Kadlubar FF (1989) Metabolic oxidation of the carcinogens 4-aminobiphenyl and 4,4′ -methylene-bis(2-chloroaniline) by human hepatic microsomes and by purified rat hepatic cytochrome P-450 monooxygenases. Cancer Res 49:25–31

    CAS  PubMed  Google Scholar 

  4. Gu L, Gonzalez FJ, Kalow W, Tang BK (1992) Biotransformation of caffeine, paraxanthine, theobromine and theophylline by cDNA-expressed human CYP1A2 and CYP2E1. Pharmacogenetics 2:73–77

    CAS  PubMed  Google Scholar 

  5. Lemoine A, Gautier JC, Azoulay D, Kiffel L, Belloc C, Guengerich FP, Maurel P, Beaune P, Leroux JP (1993) Major pathway of imipramine metabolism is catalyzed by cytochromes P-450 1A2 and P-450 3A4 in human liver. Mol Pharmacol 43:827–832

    CAS  PubMed  Google Scholar 

  6. McManus ME, Burgess WM, Veronese ME, Huggett A, Quattrochi LC, Tukey RH (1990) Metabolism of 2-acetylaminofluorene and benzo(a)pyrene and activation of food-derived heterocyclic amine mutagens by human cytochromes P-450. Cancer Res 50:3367–3376

    CAS  PubMed  Google Scholar 

  7. Nelson DR, Koymans L, Kamataki T, Stegeman JJ, Feyereisen R, Waxman DJ, Waterman MR, Gotoh O, Coon MJ, Estabrook RW, Gunsalus IC, Nebert DW (1996) P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics 6:1–42

    CAS  PubMed  Google Scholar 

  8. Minchin RF, McManus ME, Boobis AR, Davies DS, Thorgeirsson SS (1985) Polymorphic metabolism of the carcinogen 2-acetylaminofluorene in human liver microsomes. Carcinogenesis 6:1721–1724

    CAS  PubMed  Google Scholar 

  9. Shader RI, Granda BW, von Moltke LL, Giancarlo GM, Greenblatt DJ (1999) Inhibition of human cytochrome P450 isoforms in vitro by zafirlukast. Biopharm Drug Dispos 20:385–388

    Google Scholar 

  10. Nakajima M, Yokoi T, Mizutani M, Shin S, Kadlubar FF, Kamataki T (1994) Phenotyping of CYP1A2 in Japanese population by analysis of caffeine urinary metabolites: absence of mutation prescribing the phenotype in the CYP1A2 gene. Cancer Epidemiol Biomarkers Prev 3:413–421

    CAS  PubMed  Google Scholar 

  11. Tantcheva-Poor I, Zaigler M, Rietbrock S, Fuhr U (1999) Estimation of cytochrome P-450 CYP1A2 activity in 863 healthy Caucasians using a saliva-based caffeine test. Pharmacogenetics 9:131–144

    PubMed  Google Scholar 

  12. Welfare MR, Aitkin M, Bassendine MF, Daly AK (1999) Detailed modelling of caffeine metabolism and examination of the CYP1A2 gene: lack of a polymorphism in CYP1A2 in Caucasians. Pharmacogenetics 9:367–375

    CAS  PubMed  Google Scholar 

  13. Han XM, Chen XP, Wu QN, Jiang CH, Zhou HH (2000) G-2964A and C734A genetic polymorphisms of CYP1A2 in Chinese population. Acta Pharmacol Sin 21:1031–1034

    CAS  PubMed  Google Scholar 

  14. Nakajima M, Yokoi T, Mizutani M, Kinoshita M, Funayama M, Kamataki T (1999) Genetic polymorphism in the 5′ -flanking region of human CYP1A2 gene: effect on the CYP1A2 inducibility in humans. J Biochem 125:803–808

    CAS  PubMed  Google Scholar 

  15. Sachse C, Brockmoller J, Bauer S, Roots I (1999) Functional significance of a C→A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine. Br J Clin Pharmacol 47:445–449

    Article  CAS  PubMed  Google Scholar 

  16. Han XM, Ou-Yang DS, Lu PX, Jiang CH, Shu Y, Chen XP, Tan ZR, Zhou HH (2001) Plasma caffeine metabolite ratio (17X/137X) in vivo associated with G-2964A and C734A polymorphisms of human CYP1A2. Pharmacogenetics 11:429–435

    Article  CAS  PubMed  Google Scholar 

  17. Hamdy SI, Hiratsuka M, Narahara K, Endo N, El-Enany M, Moursi N, Ahmed MS, Mizugaki M (2003) Genotyping of four genetic polymorphisms in the CYP1A2 gene in the Egyptian population. Br J Clin Pharmacol 55:321–4

    Article  CAS  PubMed  Google Scholar 

  18. Sachse C, Bhambra U, Smith G, Lightfoot TJ, Barrett JH, Scollay J, Garner RC, Boobis AR, Wolf CR, Gooderham NJ (2003) Polymorphisms in the cytochrome P450 CYP1A2 gene (CYP1A2) in colorectal cancer patients and controls: allele frequencies, linkage disequilibrium and influence on caffeine metabolism. Br J Clin Pharmacol 55:68–76

    Article  CAS  PubMed  Google Scholar 

  19. Fuhr U, Rost KL (1994) Simple and reliable CYP1A2 phenotyping by the paraxanthine/caffeine ratio in plasma and in saliva. Pharmacogenetics 4:109–116

    CAS  PubMed  Google Scholar 

  20. Tang BK, Zhou Y, Kadar D, Kalow W (1994) Caffeine as a probe for CYP1A2 activity: potential influence of renal factors on urinary phenotypic trait measurements. Pharmacogenetics 4:117–124

    CAS  PubMed  Google Scholar 

  21. van Schie RC, Wilson ME (1997) Saliva: a convenient source of DNA for analysis of bi-allelic polymorphisms of Fc gamma receptor IIA (CD32) and Fc gamma receptor IIIB (CD16). J Immunol Methods 208:91–101

    Article  PubMed  Google Scholar 

  22. Mihara K, Suzuki A, Kondo T, Yasui N, Furukori H, Nagashima U, Ono S, Kaneko S, Otani K, Inoue Y (2000) Effect of a genetic polymorphism of CYP1A2 inducibility on the steady state plasma concentrations of haloperidol and reduced haloperidol in Japanese patients with schizophrenia. Ther Drug Monit 22:245–249

    Article  CAS  PubMed  Google Scholar 

  23. Shimoda K, Someya T, Morita S, Hirokane G, Yokono A, Takahashi S, Okawa M (2002) Lack of impact of CYP1A2 genetic polymorphism (C/A polymorphism at position 734 in intron 1 and G/A polymorphism at position −2964 in the 5′-flanking region of CYP1A2) on the plasma concentration of haloperidol in smoking male Japanese with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 26:261–265

    Article  CAS  PubMed  Google Scholar 

  24. Caraco Y (1998) Genetic determinants of drug responsiveness and drug interactions. Ther Drug Monit 20:517–524

    Article  CAS  PubMed  Google Scholar 

  25. Happich D, Schwaab R, Hanfland P, Hoernschemeyer D (1999) Allelic discrimination of factor V Leiden using a 5′-nuclease assay. Thromb Haemost 82:1294–1296

    CAS  PubMed  Google Scholar 

  26. Yuan CC, Peterson RJ, Wang CD, Goodsaid F, Waters DJ (2000) 5′ Nuclease assays for the loci CCR5-+/Delta32, CCR2-V64I, and SDF1-G801A related to pathogenesis of AIDS. Clin Chem 46:24–30

    CAS  PubMed  Google Scholar 

  27. Bartoli A, Xiaodong S, Gatti G, Cipolla G, Marchiselli R, Perucca E (1996) The influence of ethnic factors and gender on CYP1A2-mediated drug disposition: a comparative study in Caucasian and Chinese subjects using phenacetin as a marker substrate. Ther Drug Monit 18:586–591

    CAS  PubMed  Google Scholar 

  28. Campbell ME, Spielberg SP, Kalow W (1987) A urinary metabolite ratio that reflects systemic caffeine clearance. Clin Pharmacol Ther 42:157–165

    CAS  PubMed  Google Scholar 

  29. Kalow W, Tang BK (1991) Use of caffeine metabolite ratios to explore CYP1A2 and xanthine oxidase activities. Clin Pharmacol Ther 50:508–519

    CAS  PubMed  Google Scholar 

  30. Tanigawara Y, Kita T, Hirono M, Sakaeda T, Komada F, Okumura K (2001) Identification of N-acetyltransferase 2 and CYP2C19 genotypes for hair, buccal cell swabs, or fingernails compared with blood. Ther Drug Monit 23:341–346

    Article  CAS  PubMed  Google Scholar 

  31. van Schie RC, Wilson ME (2000) Evaluation of human FcgammaRIIA (CD32) and FcgammaRIIIB (CD16) polymorphisms in Caucasians and African-Americans using salivary DNA. Clin Diagn Lab Immunol 7:676–681

    Article  PubMed  Google Scholar 

  32. Anderson TD, Ross JP, Roby RK, Lee DA, Holland MM (1999) A validation study for the extraction and analysis of DNA from human nail material and its application to forensic casework. J Forensic Sci 44:1053–1056

    CAS  PubMed  Google Scholar 

  33. Lijnen I, Willems G (2001) DNA research in forensic dentistry. Methods Find Exp Clin Pharmacol 23:511–517

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank Dr. Raija Lindbergh for her generous help. This work was supported by a grant from the Swiss National Science Foundation to S.K. (31-59812.99).

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Division of Clinical Pharmacology and Toxicology, University Hospital, 4031 , Basel, Switzerland

    Liliane Todesco, Michael Török, Stephan Krähenbühl & Markus Wenk

Authors
  1. Liliane Todesco
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Török
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stephan Krähenbühl
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Markus Wenk
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Markus Wenk.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Todesco, L., Török, M., Krähenbühl, S. et al. Determination of −3858G→A and −164C→A genetic polymorphisms of CYP1A2 in blood and saliva by rapid allelic discrimination: large difference in the prevalence of the −3858G→A mutation between Caucasians and Asians. Eur J Clin Pharmacol 59, 343–346 (2003). https://doi.org/10.1007/s00228-003-0623-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-003-0623-1

Keywords

Search

Navigation