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Induction of CYP1A2 by heavy coffee consumption is associated with the CYP1A2 −163C>A polymorphism

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

Abstract

Objectives

To investigate the association of CYP1A2 genetic polymorphisms with the inducing effect of heavy coffee consumption on CYP1A2 activity in Serbian and Swedish populations, and to determine the frequency of the CYP1A2 genetic polymorphisms in Serbs.

Methods

Using PCR-RFLP and the tag-array minisequencing method, 126 Serbian healthy volunteers were genotyped for −3860G>A, −2467delT, −739T>G, −729C>T, −163C>A, 2159G>A, and 4795G>A. For 64 nonsmoking participants, the data on CYP1A2 activity (plasma paraxanthine/caffeine ratio) and coffee consumption habit were available from our previous study. The data on CYP1A2 genotype, enzyme activity, and coffee consumption from 114 Swedish healthy nonsmoking subjects were included in the analyses.

Results

In Serbs, CYP1A2 polymorphisms −3860G>A, −2467delT, −739T>G, −729C>T, −163C>A, and 2159G>A were found at the frequencies of 0.4, 5.0, 3.4, 0.7, 61.1, and 56.0%, respectively, while 4795G>A was not detected. Significant association of heavy coffee consumption with high CYP1A2 enzyme activity was observed only in carriers of −163 A/A. Increasing effect of −163C>A on CYP1A2 inducibility was found in both Serbian (P = 0.022) and Swedish (P = 0.016) nonsmoking heavy coffee consumers. There was no significant difference in CYP1A2 enzyme activity among genotypes in non–heavy coffee consumers. The results indicate that 22 and 14% of the phenotypic variability among Serbian and Swedish heavy coffee consumers, respectively, might be explained by −163C>A polymorphism.

Conclusions

CYP1A2 polymorphism −163C>A has an important increasing effect on CYP1A2 inducibility by heavy coffee consumption and may possibly be a contributing factor for interindividual variations in CYP1A2 enzyme activity.

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Acknowledgments

Authors would like to thank all volunteers who participated in the study. We are very grateful to Lilleba Bohman, Takashi Fukasawa, and Lili Milani for both technical support in the laboratory and scientific collaboration. The study was financially supported by the Swedish Research Council, Medicine, 3902; the Medical Faculty, University of Kragujevac, Republic of Serbia, JP 1/05; the Swedish Institute; Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I+D+I), Instituto de Salud Carlos III, Subdirección General de Evaluación y Fomento de la Investigación, PI071152; and Ayudas para la consolidación y apoyo a grupos de investigación de Extremadura, GRU09015 (Orden de 17 de diciembre de 2008, DOE 5 de enero de 2009).

Conflict of interest statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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Authors and Affiliations

  1. Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, C1: 68 SE-141 86, Stockholm, Sweden

    Natasa Djordjevic, Roza Ghotbi & Eleni Aklillu

  2. Department of Pharmacology and Toxicology, Medical Faculty, University of Kragujevac, Svetozara Markovica 69, 34 000, Kragujevac, Serbia

    Natasa Djordjevic & Slobodan Jankovic

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  1. Natasa Djordjevic
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  2. Roza Ghotbi
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  4. Eleni Aklillu
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Correspondence to Eleni Aklillu.

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Djordjevic, N., Ghotbi, R., Jankovic, S. et al. Induction of CYP1A2 by heavy coffee consumption is associated with the CYP1A2 −163C>A polymorphism. Eur J Clin Pharmacol 66, 697–703 (2010). https://doi.org/10.1007/s00228-010-0823-4

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  • DOI: https://doi.org/10.1007/s00228-010-0823-4

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