Investigating the impact of genetic variability of CYP1A2, ADORA2A, and AHR on caffeine consumption and responses in New Zealanders : a thesis presented in partial fulfilment of the requirements for the degree of Master of Science in Nutrition and Dietetics at Massey University, Albany, New Zealand
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Background: Single nucleotide polymorphisms (SNPs), in three genes encoding for cytochrome P450 1A2 (CYP1A2; rs762551), adenosine A2A receptor (ADORA2A; rs5751876), and aryl-hydrocarbon receptor (AHR; rs4410790) are known to have links to caffeine consumption and metabolism, and its resultant effects. Exploration of the links between genetic profile and caffeine response will advance understanding of the impact of caffeine consumption on individuals with differing genetic profiles. Aim: To examine caffeine consumption patterns and post-consumption responses among New Zealand (NZ) individuals and how these differ with genetic variation of CYP1A2, ADORA2A, and AHR. Methods: Caffeine intake and post-consumption responses were assessed using a caffeine consumption habits questionnaire (CaffCo). Genetic data for the SNPs (CYP1A2, ADORA2A, AHR) was analysed using MassARRAY analysis on DNA extracted from saliva samples. CaffCo data was examined according to genotype for the three SNPs, which were then paired to consider links between genes. Results: 255 participants aged 15 years and over were included in the study. Half (49.4%) of all participants were “fast” metabolisers (CYP1A2 AA) and 10.2% “ultra-slow” metabolisers (CYP1A2 CC) of caffeine. Almost half of the participants carried ADORA2A CT (46.3%), followed by CC (29.0%), and TT (24.7%). Half (51.8%) of the participants carried AHR CT, followed by CC (30.6%), and TT (17.6%) genotypes. Overall, 14.1% of participants reported a caffeine intake >400 mg/day and 52.9% an intake of 80-400 mg/day. Carriers of the genotype ADORA2A TT consumed 65 mg/day less caffeine than carriers of the heterozygote genotype (ADORA2A CT; p= 0.034). No association was found with the other analysed SNPs. Conclusions: This novel research is the first in New Zealand to examine all three genes, identifying the genetic variation and caffeine consumption habits in this population. The data show an association between ADORA2A TT and decreased caffeine consumption in this population. Future studies are needed to assess caffeine response in relation to these three genes, to understand and develop appropriate strategies for informing genotype based advice on caffeine use.
Caffeine, Metabolism, Genetic aspects, Caffeine habit, New Zealand