The mechanisms underlying caffeine’s acute effects and withdrawal symptoms are not entirely understood. The purpose was to determine whether the clusters of acute effects or withdrawal symptoms are associated with genetic polymorphisms in DARPP-32 and COMT, which mediate some of caffeine’s physiological effects. Subjects (n=1135) were from the Toronto Nutrigenomics and Healthy Study. Fourteen well-described acute effects of caffeine co-exist in six groups, while fourteen well-characterized withdrawal symptoms co-exist in three groups. Neither the rs907094 C>T polymorphism in the PPP1R1B gene encoding DARPP-32, nor the COMT Val158Met affected the odds of reporting any acute effects or withdrawal symptoms cluster. Among individuals consuming ≥ 200 mg/d of caffeine, Met/Met homozygotes were more likely to report the “increased heart rate” acute effects cluster. These results suggest that ‘slow’ COMT activity, conferred by the Met allele, may explain part of the inter-individual variability in the risk for increased heart rate among heavy caffeine consumers.

The mechanisms underlying caffeine’s acute effects and withdrawal symptoms are not entirely understood. The purpose was to determine whether the clusters of acute effects or withdrawal symptoms are associated with genetic polymorphisms in DARPP-32 and COMT, which mediate some of caffeine’s physiological effects. Subjects (n=1135) were from the Toronto Nutrigenomics and Healthy Study. Fourteen well-described acute effects of caffeine co-exist in six groups, while fourteen well-characterized withdrawal symptoms co-exist in three groups. Neither the rs907094 C>T polymorphism in the PPP1R1B gene encoding DARPP-32, nor the COMT Val158Met affected the odds of reporting any acute effects or withdrawal symptoms cluster. Among individuals consuming ≥ 200 mg/d of caffeine, Met/Met homozygotes were more likely to report the “increased heart rate” acute effects cluster. These results suggest that ‘slow’ COMT activity, conferred by the Met allele, may explain part of the inter-individual variability in the risk for increased heart rate among heavy caffeine consumers.