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11Polymorphisms impairing histamine degradation moderate behavioural responses to food additive challenge

Background: the relationship between artificial food colouring and benzoate perservative (AFCP) intake and behaviour has hitherto been contentious. We have previously shown in a population based DBPCFC study, an adverse effect of AFCP on parentally-rated behaviour of 3 year olds and have now confirmed the observations in 144 8Y9 year olds and 153 3 year olds using objective measures of observed behaviours in a school setting. One potential mechanism is IgE independent histamine release from circulating basophils. Methods: from the second challenge study we have genotyped the children using buccal cells and related findings to the magnitude of the behavioural response to challenge. Results: polymorphisms of catecholamine genes, COMT Val108Met and ADRA2A C1291G, previously associated with ADHD, had no impact on responses but T939C and Thr105Ile polymorphisms of the histamine Nmethyltransferase gene (HNMT) significantly (p=0.02 and 0.04 respectively) adversely affected responses to AFCP challenge. Conclusion: HNMT polymorphisms impair histamine clearance and AFCP cause histamine release. The presence of Histamine 3 receptors in the brain provides a potential mechanism (and therapeutic target) to explain the effect we observed. Many environmental factors increase histamine including infections and many foods. This would explain the frequent claim that food intolerance and infections adversely affect behaviour in some children. This gene by environment interaction should be investigated in relation to AFCP induced urticaria, asthma and other atopic conditions.