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<br/>circulating basophils.<br/>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.<br/>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<br/>gene (HNMT) significantly (p=0.02 and 0.04 respectively)<br/>adversely affected responses to AFCP challenge.<br/>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<br/>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<br/>gene by environment interaction should be investigated in relation to AFCP induced urticaria, asthma and other atopic conditions
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