Genetic Modifiers of Caffeine Consumption and Risk of Myocardial Infarction

The variability in caffeine consumption and inconsistencies among studies linking caffeine to heart disease may be explained by genetic variation. Caffeine antagonizes adenosine receptors with downstream effects on dopamine and serotonin. The objectives of this thesis were to determine whether the DRD2 957C>T or HTR2A 102C>T polymorphisms are associated with caffeine consumption or modify the association between coffee consumption and risk of myocardial infarction (MI). DRD2 genotype was associated with caffeine consumption among non-smokers and CYP1A2 -163C allele carriers. HTR2A genotype was associated with caffeine consumption among non-smokers and subjects with the ADORA2A TT genotype. Neither polymorphism modified the association between coffee consumption and risk of MI; however, a significant coffee x HTR2A interaction was seen among subjects with the CYP1A2 -163C allele. The results suggest caffeine’s reinforcing effects may be mediated by the dopamine and serotonin receptors and implicate serotonin in caffeine’s effect on risk of MI.MAS