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European Journal of Clinical Pharmacology

, Volume 66, Issue 7, pp 697–703 | Cite as

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

  • Natasa Djordjevic
  • Roza Ghotbi
  • Slobodan Jankovic
  • Eleni AklilluEmail author
Pharmacogenetics

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.

Keywords

CYP1A2 Polymorphisms Induction Coffee 

Notes

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.

References

  1. 1.
    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 3:413–421PubMedGoogle Scholar
  2. 2.
    Zhou SF, Wang B, Yang LP, Liu JP (2010) Structure, function, regulation and polymorphism and the clinical significance of human cytochrome P450 1A2. Drug Metab Rev (in press)Google Scholar
  3. 3.
    Bageman E, Ingvar C, Rose C, Jernstrom H (2008) Coffee consumption and CYP1A2*1F genotype modify age at breast cancer diagnosis and estrogen receptor status. Cancer Epidemiol Biomarkers Prev 17:895–901CrossRefPubMedGoogle Scholar
  4. 4.
    Palatini P, Ceolotto G, Ragazzo F, Dorigatti F, Saladini F, Papparella I, Mos L, Zanata G, Santonastaso M (2009) CYP1A2 genotype modifies the association between coffee intake and the risk of hypertension. J Hypertens 27:1594–1601CrossRefPubMedGoogle Scholar
  5. 5.
    Aklillu E, Carrillo JA, Makonnen E, Hellman K, Pitarque M, Bertilsson L, Ingelman-Sundberg M (2003) Genetic polymorphism of CYP1A2 in Ethiopians affecting induction and expression: characterization of novel haplotypes with single-nucleotide polymorphisms in intron 1. Mol Pharmacol 64:659–669CrossRefPubMedGoogle Scholar
  6. 6.
    Kashuba AD, Bertino JS Jr, Kearns GL, Leeder JS, James AW, Gotschall R, Nafziger AN (1998) Quantitation of three-month intraindividual variability and influence of sex and menstrual cycle phase on CYP1A2, N-acetyltransferase-2, and xanthine oxidase activity determined with caffeine phenotyping. Clin Pharmacol Ther 63:540–551CrossRefPubMedGoogle Scholar
  7. 7.
    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 47:445–449CrossRefPubMedGoogle Scholar
  8. 8.
    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 125:803–808PubMedGoogle Scholar
  9. 9.
    Djordjevic N, Ghotbi R, Bertilsson L, Jankovic S, Aklillu E (2008) Induction of CYP1A2 by heavy coffee consumption in Serbs and Swedes. Eur J Clin Pharmacol 64:381–385CrossRefPubMedGoogle Scholar
  10. 10.
    Ghotbi R, Christensen M, Roh HK, Ingelman-Sundberg M, Aklillu E, Bertilsson L (2007) Comparisons of CYP1A2 genetic polymorphisms, enzyme activity and the genotype-phenotype relationship in Swedes and Koreans. Eur J Clin Pharmacol 63:537–546CrossRefPubMedGoogle Scholar
  11. 11.
    Chida M, Yokoi T, Fukui T, Kinoshita M, Yokota J, Kamataki T (1999) Detection of three genetic polymorphisms in the 5′-flanking region and intron 1 of human CYP1A2 in the Japanese population. Jpn J Cancer Res 90:899–902PubMedGoogle Scholar
  12. 12.
    Han XM, Ouyang DS, Chen XP, Shu Y, Jiang CH, Tan ZR, Zhou HH (2002) Inducibility of CYP1A2 by omeprazole in vivo related to the genetic polymorphism of CYP1A2. Br J Clin Pharmacol 54:540–543CrossRefPubMedGoogle Scholar
  13. 13.
    Parker AC, Pritchard P, Preston T, Choonara I (1998) Induction of CYP1A2 activity by carbamazepine in children using the caffeine breath test. Br J Clin Pharmacol 45:176–178CrossRefPubMedGoogle Scholar
  14. 14.
    Fuhr U, Anders EM, Mahr G, Sorgel F, Staib AH (1992) Inhibitory potency of quinolone antibacterial agents against cytochrome P450IA2 activity in vivo and in vitro. Antimicrob Agents Chemother 36:942–948PubMedGoogle Scholar
  15. 15.
    Gunes A, Ozbey G, Vural EH, Uluoglu C, Scordo MG, Zengil H, Dahl ML (2009) Influence of genetic polymorphisms, smoking, gender and age on CYP1A2 activity in a Turkish population. Pharmacogenomics 10:769–778CrossRefPubMedGoogle Scholar
  16. 16.
    Djordjevic N, Carrillo JA, Gervasini G, Jankovic S, Aklillu E (2010) In vivo evaluation of CYP2A6 and xanthine oxidase enzyme activities in the Serbian population. Eur J Clin Pharmacol (in press)Google Scholar
  17. 17.
    Lindroos K, Sigurdsson S, Johansson K, Ronnblom L, Syvanen AC (2002) Multiplex SNP genotyping in pooled DNA samples by a four-colour microarray system. Nucleic Acids Res 30:e70CrossRefPubMedGoogle Scholar
  18. 18.
    Chevalier D, Cauffiez C, Allorge D, Lo-Guidice JM, Lhermitte M, Lafitte JJ, Broly F (2001) Five novel natural allelic variants—951A>C, 1042G>A (D348N), 1156A>T (I386F), 1217G>A (C406Y) and 1291C>T (C431Y)—of the human CYP1A2 gene in a French Caucasian population. Hum Mutat 17:355–356Google Scholar
  19. 19.
    Kootstra-Ros JE, Smallegoor W, van der Weide J (2005) The cytochrome P450 CYP1A2 genetic polymorphisms *1F and *1D do not affect clozapine clearance in a group of schizophrenic patients. Ann Clin Biochem 42:216–219CrossRefPubMedGoogle Scholar
  20. 20.
    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 55:68–76CrossRefPubMedGoogle Scholar
  21. 21.
    Pavanello S, Pulliero A, Lupi S, Gregorio P, Clonfero E (2005) Influence of the genetic polymorphism in the 5′-noncoding region of the CYP1A2 gene on CYP1A2 phenotype and urinary mutagenicity in smokers. Mutat Res 587:59–66PubMedGoogle Scholar
  22. 22.
    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 26:261–265CrossRefPubMedGoogle Scholar
  23. 23.
    Nordmark A, Lundgren S, Ask B, Granath F, Rane A (2002) The effect of the CYP1A2 *1F mutation on CYP1A2 inducibility in pregnant women. Br J Clin Pharmacol 54:504–510CrossRefPubMedGoogle Scholar
  24. 24.
    Takata K, Saruwatari J, Nakada N, Nakagawa M, Fukuda K, Tanaka F, Takenaka S, Mihara S, Marubayashi T, Nakagawa K (2006) Phenotype-genotype analysis of CYP1A2 in Japanese patients receiving oral theophylline therapy. Eur J Clin Pharmacol 62:23–28CrossRefPubMedGoogle Scholar
  25. 25.
    Krul C, Hageman G (1998) Analysis of urinary caffeine metabolites to assess biotransformation enzyme activities by reversed-phase high-performance liquid chromatography. J Chromatogr B Biomed Sci Appl 709:27–34CrossRefPubMedGoogle Scholar
  26. 26.
    Fuhr U, Jetter A, Kirchheiner J (2007) Appropriate phenotyping procedures for drug metabolizing enzymes and transporters in humans and their simultaneous use in the “cocktail” approach. Clin Pharmacol Ther 81:270–283CrossRefPubMedGoogle Scholar
  27. 27.
    Fuhr U, Rost KL (1994) Simple and reliable CYP1A2 phenotyping by the paraxanthine/caffeine ratio in plasma and in saliva. Pharmacogenetics 4:109–116CrossRefPubMedGoogle Scholar
  28. 28.
    Kalow W, Tang BK (1991) Caffeine as a metabolic probe: exploration of the enzyme-inducing effect of cigarette smoking. Clin Pharmacol Ther 49:44–48PubMedGoogle Scholar
  29. 29.
    Abernethy DR, Todd EL (1985) Impairment of caffeine clearance by chronic use of low-dose oestrogen-containing oral contraceptives. Eur J Clin Pharmacol 28:425–428CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Natasa Djordjevic
    • 1
    • 2
  • Roza Ghotbi
    • 1
  • Slobodan Jankovic
    • 2
  • Eleni Aklillu
    • 1
    Email author
  1. 1.Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska InstitutetKarolinska University Hospital, HuddingeStockholmSweden
  2. 2.Department of Pharmacology and Toxicology, Medical FacultyUniversity of KragujevacKragujevacSerbia

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