Genetics of caffeine consumption and responses to caffeine
- 3.4k Downloads
Caffeine is widely consumed in foods and beverages and is also used for a variety of medical purposes. Despite its widespread use, relatively little is understood regarding how genetics affects consumption, acute response, or the long-term effects of caffeine.
This paper reviews the literature on the genetics of caffeine from the following: (1) twin studies comparing heritability of consumption and of caffeine-related traits, including withdrawal symptoms, caffeine-induced insomnia, and anxiety, (2) association studies linking genetic polymorphisms of metabolic enzymes and target receptors to variations in caffeine response, and (3) case-control and prospective studies examining relationship between polymorphisms associated with variations in caffeine response to risks of Parkinson’s and cardiovascular diseases in habitual caffeine consumers.
Twin studies find the heritability of caffeine-related traits to range between 0.36 and 0.58. Analysis of polysubstance use shows that predisposition to caffeine use is highly specific to caffeine itself and shares little common disposition to use of other substances. Genome association studies link variations in adenosine and dopamine receptors to caffeine-induced anxiety and sleep disturbances. Polymorphism in the metabolic enzyme cytochrome P-450 is associated with risk of myocardial infarction in caffeine users.
Modeling based on twin studies reveals that genetics plays a role in individual variability in caffeine consumption and in the direct effects of caffeine. Both pharmacodynamic and pharmacokinetic polymorphisms have been linked to variation in response to caffeine. These studies may help guide future research in the role of genetics in modulating the acute and chronic effects of caffeine.
KeywordsCaffeine Adenosine Dopamine Genetic polymorphism CYP1A2 Parkinson’s cardiovascular disease
This research was supported by NIDA (DA021336 and DA02812). All authors reported no biomedical interests or potential conflicts of interest.
- Bchir F, Dogui M, Ben Fradj R, Arnaud MJ, Saguem S (2006) Differences in pharmacokinetic and electroencephalographic responses to caffeine in sleep-sensitive and non-sensitive subjects. CR Biol 329:512–519Google Scholar
- Carmelli D, Swan GE, Robinette D, Fabsitz RR (1990) Heritability of substance use in the NAS-NRC Twin Registry. Acta Genet Med Gemellol (Roma) 39:91–98Google Scholar
- Chen J-F, Xu K, Petzer JP, Staal R, Xu Y-H, Beilstein M, Sonsalla PK, Castagnoli K, Castagnoli N Jr, Schwarzschild MA (2001) Neuroprotection by caffeine and A2A adenosine receptor inactivation in a model of Parkinson’s disease. J Neurosci 21:143RCGoogle Scholar
- Ciruela F, Casado V, Rodrigues RJ, Lujan R, Burgueno J, Canals M, Borycz J, Rebola N, Goldberg SR, Mallol J, Cortes A, Canela EI, Lopez-Gimenez JF, Milligan G, Lluis C, Cunha RA, Ferre S, Franco R (2006) Presynaptic control of striatal glutamatergic neurotransmission by adenosine A1–A2A receptor heteromers. J Neurosci 26:2080–2087PubMedGoogle Scholar
- Deckert J, Nothen MM, Franke P, Delmo C, Fritze J, Knapp M, Maier W, Beckmann H, Propping P (1998) Systematic mutation screening and association study of the A1 and A2a adenosine receptor genes in panic disorder suggest a contribution of the A2a gene to the development of disease. Mol Psychiatry 3:81–85PubMedGoogle Scholar
- Dhaenens CM, Burnouf S, Simonin C, Van Brussel E, Duhamel A, Defebvre L, Duru C, Vuillaume I, Cazeneuve C, Charles P, Maison P, Debruxelles S, Verny C, Gervais H, Azulay JP, Tranchant C, Bachoud-Levi AC, Durr A, Buee L, Krystkowiak P, Sablonniere B, Blum D (2009) A genetic variation in the ADORA2A gene modifies age at onset in Huntington’s disease. Neurobiol Dis 35:474–476PubMedGoogle Scholar
- Fuxe K, Agnati LF, Jacobsen K, Hillion J, Canals M, Torvinen M, Tinner-Staines B, Staines W, Rosin D, Terasmaa A, Popoli P, Leo G, Vergoni V, Lluis C, Ciruela F, Franco R, Ferre S (2003) Receptor heteromerization in adenosine A2A receptor signaling: relevance for striatal function and Parkinson’s disease. Neurology 61:19S–23SGoogle Scholar
- Haskell CF, Kennedy DO, Wesnes KA, Scholey AB (2005) Cognitive and mood improvements of caffeine in habitual consumers and habitual non-consumers of caffeine. Psychopharmacology (Berl) 179:813–825Google Scholar
- 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 63:540–551PubMedGoogle Scholar
- Lieberman HR, Tharion WJ, Shukitt-Hale B, Speckman KL, Tulley R (2002) Effects of caffeine, sleep loss, and stress on cognitive performance and mood during U.S. Navy SEAL training. Sea–Air–Land. Psychopharmacology (Berl) 164:250–261Google Scholar
- Mosqueda-Garcia R, Robertson D, Robertson RM (1993) The cardiovascular effects of caffeine. In: Garattini S (ed) Caffeine, coffee, and health. Raven, New York, pp 157–176Google Scholar
- Neale MC, Cardon LR (1992) Methodology for genetic studies of twins and families. Kluwer, LondonGoogle Scholar
- Papamichael CM, Aznaouridis KA, Karatzis EN, Karatzi KN, Stamatelopoulos KS, Vamvakou G, Lekakis JP, Mavrikakis ME (2005) Effect of coffee on endothelial function in healthy subjects: the role of caffeine. Clin Sci (Lond) 109:55–60Google Scholar
- Perlis ML, Merica H, Smith MT, Giles DE (2001) Beta EEG activity and insomnia. Sleep Med Rev 5:365–376Google Scholar
- Rasmussen BB, Brix TH, Kyvik KO, Brøsen K (2002) The interindividual differences in the 3-demthylation of caffeine alias CYP1A2 is determined by both genetic and environmental factors. Pharmacogenet Genomics 12:473–478Google Scholar