A Casein Kinase 1 Epsilon Small Nucleotide Polymorphism and Acute Response to Caffeine in Humans
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Casein kinase 1 epsilon (CSNK 1 E) acts on the second messenger system of DARPP-32 (Dopamine-And-cAMP-Regulated-Phosphoprotein-32 kDa) and is correlated with drug sensitivity in pharmacogenetic mouse studies of the stimulant drugs cocaine and methamphetamine. Further strengthening support for this relationship between CSNKIE and drug sensitivity is a human amphetamine study which found a specific CSNKIE small nucleotide polymorphism (SNP), rs135745, to be associated with increased sensitivity to an acute dose of amphetamine in healthy volunteers. For the current study, we explored this SNP, rs135745, in relation to physiological, subjective and behavioral responses to acute ingestion of the stimulant caffeine (0, 50mg, 150mg and 450mg) in light caffeine users, under double-blind conditions. We grouped subjects according to their rs135745 genotype (GIG, G/C or C/C) and compared responses to caffeine among the three genotypic groups. F or the primary outcome measures, we found no significant correlations between genotype and acute caffeine ingestion. We did find a significant trend unrelated to acute caffeine consumption where subjects homozygous for the GIG allele exhibited significantly higher mean systolic blood pressure than heterozygous subjects (G/e). The results from this study do not support the hypothesis that the CSNKIE SNP rs135745 is associated with an acute response to caffeine.