Sequence variants at CYP1A1–CYP1A2 and AHR associate with coffee consumption
Open Access
- 28 February 2011
- journal article
- research article
- Published by Oxford University Press (OUP) in Human Molecular Genetics
- Vol. 20 (10), 2071-2077
- https://doi.org/10.1093/hmg/ddr086
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.Keywords
This publication has 29 references indexed in Scilit:
- Genome-wide association study of blood pressure and hypertensionNature Genetics, 2009
- Genome-wide association study identifies eight loci associated with blood pressureNature Genetics, 2009
- The role of the dioxin-responsive element cluster between the Cyp1a1 and Cyp1a2 loci in aryl hydrocarbon receptor biologyProceedings of the National Academy of Sciences of the United States of America, 2009
- Acute and long-term cardiovascular effects of coffee: Implications for coronary heart diseasePharmacology & Therapeutics, 2009
- Conserved genomic structure of the Cyp1a1 and Cyp1a2 loci and their dioxin responsive elements clusterBiochemical Pharmacology, 2009
- A new multipoint method for genome-wide association studies by imputation of genotypesNature Genetics, 2007
- Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPsHuman Molecular Genetics, 2006
- A novel endonuclease IV post-PCR genotyping systemNucleic Acids Research, 2006
- A haplotype map of the human genomeNature, 2005
- Quantifying heterogeneity in a meta-analysisStatistics in Medicine, 2002