A genotype describes a variant of a gene that can alter the function of the protein the gene is translated into. There are specific proteins (enzymes) in the body that metabolize caffeine and there are several variants of the genes that produce those enzymes. One enzyme, cytochrome P450 1A2, which is responsible for approximately 95% of caffeine metabolism, is coded by the CYP1A2 gene. Different variants of this gene cause people to be “slow” or “fast” metabolizers of caffeine. The current evidence shows that variants in the CYP1A2 gene may influence habitual caffeine intake[1][2] and caffeine’s effect on cognitive function.[3] While some studies implicate CYP1A2 gene variants in the effect of caffeine on sports performance, the effects are highly variable and further high-quality studies are needed.[4][5]
Variants of the ADORA2A gene, which codes the adenosine A2A receptor protein, affect caffeine’s ability to prevent adenosine binding to adenosine receptors. This causes people to have “high” or “low” caffeine sensitivity. The current evidence shows that variants in the ADORA2A gene may influence the anxiogenic (anxiety-causing)[1][3] and sleep-disturbing[3][6][7][8] effects of caffeine.
Some studies find a relationship between different CYP1A2 and ADORA2A genotypes and cardiometabolic risk factors, like blood glucose responses to a meal and blood pressure.[9] However, the current evidence suggests that different genotypes do not influence the effect of caffeine on cardiovascular disease risk.[10][11]