Sequence variants at CYP1A1-CYP1A2 and AHR associate with coffee consumption.
Journal: 2011/August - Human Molecular Genetics
ISSN: 1460-2083
Abstract:
Coffee is the most commonly used stimulant and caffeine is its main psychoactive ingredient. The heritability of coffee consumption has been estimated at around 50%. We performed a meta-analysis of four genome-wide association studies of coffee consumption among coffee drinkers from Iceland (n = 2680), The Netherlands (n = 2791), the Sorbs Slavonic population isolate in Germany (n = 771) and the USA (n = 369) using both directly genotyped and imputed single nucleotide polymorphisms (SNPs) (2.5 million SNPs). SNPs at the two most significant loci were also genotyped in a sample set from Iceland (n = 2430) and a Danish sample set consisting of pregnant women (n = 1620). Combining all data, two sequence variants significantly associated with increased coffee consumption: rs2472297-T located between CYP1A1 and CYP1A2 at 15q24 (P = 5.4 · 10(-14)) and rs6968865-T near aryl hydrocarbon receptor (AHR) at 7p21 (P = 2.3 · 10(-11)). An effect of ∼0.2 cups a day per allele was observed for both SNPs. CYP1A2 is the main caffeine metabolizing enzyme and is also involved in drug metabolism. AHR detects xenobiotics, such as polycyclic aryl hydrocarbons found in roasted coffee, and induces transcription of CYP1A1 and CYP1A2. The association of these SNPs with coffee consumption was present in both smokers and non-smokers.
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Hum Mol Genet 20(10): 2071-2077

Sequence variants at CYP1A1–CYP1A2 and AHR associate with coffee consumption

+21 authors

Supplementary Material

Supplementary Data:
deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland,
Department of Epidemiology Research, Statens Serum Institut, 2300 Copenhagen S, Denmark,
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LJ, UK,
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK,
Department of Genetics, Comprehensive Cancer Center IKO, Nijmegen 6501 BG, The Netherlands,
Department of Epidemiology, Biostatistics & HTA,
Department of Genetics,
Department of Psychiatry, and
Department of Endocrinology, Radboud University Nijmegen Medical Centre, Nijmegen 6500 HB, The Netherlands,
Interdisciplinary Centre for Clinical Research,
Department of Medicine, and
LIFE Study Center, University of Leipzig, 04103 Leipzig, Germany,
The Johns Hopkins GeneSTAR Research Program, Division of General Internal Medicine, The Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA,
University of Iceland, Faculty of Medicine, 101 Reykjavik, Iceland, and
Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, 6500 HB, The Netherlands
To whom correspondence should be addressed. Tel: +354 5702371; Fax: +354 5701903; Email: si.edoced@melus.kcirtap
Contributed by These authors contributed equally to this work.
Received 2010 Dec 6; Revised 2011 Feb 14; Accepted 2011 Feb 23.

Abstract

Coffee is the most commonly used stimulant and caffeine is its main psychoactive ingredient. The heritability of coffee consumption has been estimated at around 50%. We performed a meta-analysis of four genome-wide association studies of coffee consumption among coffee drinkers from Iceland (n = 2680), the Netherlands (n = 2791), the Sorbs Slavonic population isolate in Germany (n = 771) and the USA (n = 369) using both directly genotyped and imputed single nucleotide polymorphisms (SNPs) (2.5 million SNPs). SNPs at the two most significant loci were also genotyped in a sample set from Iceland (n = 2430) and a Danish sample set consisting of pregnant women (n = 1620). Combining all data, two sequence variants significantly associated with increased coffee consumption: rs2472297-T located between CYP1A1 and CYP1A2 at 15q24 (P = 5.4 · 10) and rs6968865-T near aryl hydrocarbon receptor (AHR) at 7p21 (P = 2.3 · 10). An effect of ∼0.2 cups a day per allele was observed for both SNPs. CYP1A2 is the main caffeine metabolizing enzyme and is also involved in drug metabolism. AHR detects xenobiotics, such as polycyclic aryl hydrocarbons found in roasted coffee, and induces transcription of CYP1A1 and CYP1A2. The association of these SNPs with coffee consumption was present in both smokers and non-smokers.

Abstract

Results are given for the four genome-wide association sample sets and two follow-up sample sets. Shown are the number of coffee drinkers (n), fraction of coffee drinkers that are males (male), their mean age and standard deviation (age and SD), the fraction of the individuals queried that are coffee drinkers (drink coffee), the mean and SD of the coffee consumption in cups per day for males and females (consumption and SD), the allele frequencies (freq), the estimated allelic effects on coffee consumption and its 95% CI in cups per day (effect and 95% CI), the P-value for the test of association (P-value) and the SNP genotyping imputation information (Gtd for directly genotyped SNPs).

*P-values were combined using the weighted z-scores.

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REFERENCES

REFERENCES

References

  • 1. van Dam R.MCoffee consumption and risk of type 2 diabetes, cardiovascular diseases, and cancer. Appl. Physiol. Nutr. Metab. 2008;33:1269–1283.[PubMed][Google Scholar]
  • 2. Snyder S.H., Katims J.J., Annau Z., Bruns R.F., Daly J.WAdenosine receptors and behavioral actions of methylxanthines. Proc. Natl Acad. Sci. USA. 1981;78:3260–3264.[Google Scholar]
  • 3. Cnattingius S., Signorello L.B., Anneren G., Clausson B., Ekbom A., Ljunger E., Blot W.J., McLaughlin J.K., Petersson G., Rane A., et al Caffeine intake and the risk of first-trimester spontaneous abortion. N. Engl. J. Med. 2000;343:1839–1845.[PubMed][Google Scholar]
  • 4. Riksen N.P., Rongen G.A., Smits PAcute and long-term cardiovascular effects of coffee: implications for coronary heart disease. Pharmacol. Ther. 2009;121:185–191.[PubMed][Google Scholar]
  • 5. Rosso A., Mossey J., Lippa C.FCaffeine: neuroprotective functions in cognition and Alzheimer's disease. Am. J. Alzheimers Dis. Other Demen. 2008;23:417–422.[PubMed][Google Scholar]
  • 6. Kawachi I., Willett W.C., Colditz G.A., Stampfer M.J., Speizer F.EA prospective study of coffee drinking and suicide in women. Arch. Intern. Med. 1996;156:521–525.[PubMed][Google Scholar]
  • 7. Carmelli D., Swan G.E., Robinette D., Fabsitz R.RHeritability of substance use in the NAS-NRC Twin Registry. Acta Genet. Med. Gemellol. (Roma) 1990;39:91–98.[PubMed][Google Scholar]
  • 8. Laitala V.S., Kaprio J., Silventoinen KGenetics of coffee consumption and its stability. Addiction. 2008;103:2054–2061.[PubMed][Google Scholar]
  • 9. Vink J.M., Staphorsius A.S., Boomsma D.IA genetic analysis of coffee consumption in a sample of Dutch twins. Twin Res. Hum. Genet. 2009;12:127–131.[PubMed][Google Scholar]
  • 10. A haplotype map of the human genome. Nature. 2005;437:1299–1320.
  • 11. Rodrigues A.DIntegrated cytochrome P450 reaction phenotyping: attempting to bridge the gap between cDNA-expressed cytochromes P450 and native human liver microsomes. Biochem. Pharmacol. 1999;57:465–480.[PubMed][Google Scholar]
  • 12. Faber M.S., Jetter A., Fuhr UAssessment of CYP1A2 activity in clinical practice: why, how, and when? Basic Clin. Pharmacol. Toxicol. 2005;97:125–134.[PubMed][Google Scholar]
  • 13. Nukaya M., Bradfield C.AConserved genomic structure of the Cyp1a1 and Cyp1a2 loci and their dioxin responsive elements cluster. Biochem. Pharmacol. 2009;77:654–659.[Google Scholar]
  • 14. Nukaya M., Moran S., Bradfield C.AThe role of the dioxin-responsive element cluster between the Cyp1a1 and Cyp1a2 loci in aryl hydrocarbon receptor biology. Proc. Natl Acad. Sci. USA. 2009;106:4923–4928.[Google Scholar]
  • 15. Sachse C., Brockmoller J., Bauer S., Roots IFunctional significance of a C->A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine. Br. J. Clin. Pharmacol. 1999;47:445–449.[Google Scholar]
  • 16. Djordjevic N., Ghotbi R., Bertilsson L., Jankovic S., Aklillu EInduction of CYP1A2 by heavy coffee consumption in Serbs and Swedes. Eur. J. Clin. Pharmacol. 2008;64:381–385.[PubMed][Google Scholar]
  • 17. Tantcheva-Poor I., Zaigler M., Rietbrock S., Fuhr UEstimation of cytochrome P-450 CYP1A2 activity in 863 healthy Caucasians using a saliva-based caffeine test. Pharmacogenetics. 1999;9:131–144.[PubMed][Google Scholar]
  • 18. Saccone S.F., Hinrichs A.L., Saccone N.L., Chase G.A., Konvicka K., Madden P.A., Breslau N., Johnson E.O., Hatsukami D., Pomerleau O., et al Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs. Hum. Mol. Genet. 2007;16:36–49.[Google Scholar]
  • 19. Thorgeirsson T.E., Geller F., Sulem P., Rafnar T., Wiste A., Magnusson K.P., Manolescu A., Thorleifsson G., Stefansson H., Ingason A., et al A variant associated with nicotine dependence, lung cancer and peripheral arterial disease. Nature. 2008;452:638–642.[Google Scholar]
  • 20. Newton-Cheh C., Johnson T., Gateva V., Tobin M.D., Bochud M., Coin L., Najjar S.S., Zhao J.H., Heath S.C., Eyheramendy S., et al Genome-wide association study identifies eight loci associated with blood pressure. Nat. Genet. 2009;41:666–676.[Google Scholar]
  • 21. Levy D., Ehret G.B., Rice K., Verwoert G.C., Launer L.J., Dehghan A., Glazer N.L., Morrison A.C., Johnson A.D., Aspelund T., et al Genome-wide association study of blood pressure and hypertension. Nat. Genet. 2009;41:677–687.[Google Scholar]
  • 22. Carrillo J.A., Benitez JCYP1A2 activity, gender and smoking, as variables influencing the toxicity of caffeine. Br. J. Clin. Pharmacol. 1996;41:605–608.[Google Scholar]
  • 23. Kiemeney L.A., Thorlacius S., Sulem P., Geller F., Aben K.K., Stacey S.N., Gudmundsson J., Jakobsdottir M., Bergthorsson J.T., Sigurdsson A., et al Sequence variant on 8q24 confers susceptibility to urinary bladder cancer. Nat. Genet. 2008;40:1307–1312.[Google Scholar]
  • 24. Kutyavin I.V., Milesi D., Belousov Y., Podyminogin M., Vorobiev A., Gorn V., Lukhtanov E.A., Vermeulen N.M., Mahoney WA novel endonuclease IV post-PCR genotyping system. Nucleic Acids Res. 2006;34:e128.[Google Scholar]
  • 25. Marchini J., Howie B., Myers S., McVean G., Donnelly PA new multipoint method for genome-wide association studies by imputation of genotypes. Nat. Genet. 2007;39:906–913.[PubMed][Google Scholar]
  • 26. Gretarsdottir S., Thorleifsson G., Reynisdottir S.T., Manolescu A., Jonsdottir S., Jonsdottir T., Gudmundsdottir T., Bjarnadottir S.M., Einarsson O.B., Gudjonsdottir H.M., et al The gene encoding phosphodiesterase 4D confers risk of ischemic stroke. Nat. Genet. 2003;35:131–138.[PubMed][Google Scholar]
  • 27. Rice J.A Mathematical Statistics and Data Analysis. Belmont, CA: Wadsworth Inc.; 1995. [PubMed][Google Scholar]
  • 28. Devlin B., Roeder KGenomic control for association studies. Biometrics. 1999;55:997–1004.[PubMed][Google Scholar]
  • 29. Higgins J.P., Thompson S.GQuantifying heterogeneity in a meta-analysis. Stat. Med. 2002;21:1539–1558.[PubMed][Google Scholar]
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