Gene‐diet interaction and dementia risk: The example of coffee and CYP1A2 gene

Abstract

AbstractBackgroundCoffee consumption has been associated with a decreased risk of dementia, although findings have been inconsistent. Among the numerous coffee bioactives, caffeine may improve neurotransmission by acting as antagonist of adenosine receptors. There exists a large inter‐individual variability in caffeine metabolism in relation to the cytochrome P450 1A2 (CYP1A2), and some studies suggest that specific genes of CYP1A2 may module the relationship between coffee and chronic diseases (cancer, cardiovascular disease, Parkinson’s disease). Our objective was to evaluate the association between coffee consumption and dementia risk in the French Three‐City (3C) cohort of older persons, taking into account the potential modulatory effect of CYP1A2 rs762551 genotype.MethodWe included 5,963 participants, free of dementia at baseline when they reported their daily coffee consumption and who were followed for incidence dementia up to 14 years. All included participants had available genome‐wide genotyping. We tested the interaction between coffee consumption (number of cups/day) and CYP1A2 rs762551 (number of alternative allele C) on the risk of dementia using Cox proportional hazard models adjusted for age (as time scale), sex, level of education and ApoE‐ε4. Multivariate associations between coffee consumption and the risk of dementia were then investigated according to CYP1A2 rs762551 genotype that induce “faster” caffeine metabolism (A/A) or “slower” caffeine metabolism (C/A‐C/C).ResultParticipants were 74 (sd 5) years‐old on average at baseline and 61% were women. The mean coffee consumption was 1.6 cups/day (sd 1.3; min 0; max 10 cups/d) and 78% of participants reported the consumption of at least 1 cup/d. In total, 52% of participants were carriers of at least one rs762551 C allele. Over a median follow‐up of 8.6 years, 756 cases of dementia were diagnosed. Daily coffee consumption was associated with a decreased risk of dementia only among carriers of the CYP1A2 rs762551 C allele, with each additional cup of coffee being associated with a 10% reduced risk of dementia (95%CI: 2‐18%; p for interaction=0.007).ConclusionIn our study, coffee consumption was associated with a reduced risk of dementia among older persons with a genetic predisposition towards a slow caffeine metabolism.