T07039: Determination of the role of an activating c-kit mutation in food anaphylaxis

Study Duration: June 2003 to December 2003

Contractor: Central Science Laboratory

This proposal is based upon preliminary data, which came from screening food allergic and non-food allergic individuals. If a link between an activating mutation in the c-kit oncogene and the risk of developing severe food allergy is established, this study could form the basis of larger scale studies to correlate this mutation with the risk of anaphylaxis in a range of food allergens. The proposal falls within the FSA remit in providing the mechanism by which at risk individuals can be identified both for targeted advice and in FSA-funded studies into food allergy.

This project is studying four well-defined subject groups in statistically significant cohorts to confirm these preliminary results. Suitable patients have been identified and blood samples taken and analysed for the presence of c-kit mutations. Sequencing results will be compared with information about the allergic status of the subject, and a link between the presence of a mutation and the occurrence of anaphylaxis will be determined statistically.

The aim of this study was to determine if the same genetic alteration found in mastocytosis patients could be identified in blood cells taken from severely allergic individuals who had previously experienced an anaphylactic reaction.

Forty-one volunteers were recruited, representing four clinical groups; 1) healthy normals, 2) subjects with minor allergic conditions such as hayfever and eczema, 3) subjects with a well documented history of anaphylaxis to a specific food type, and 4) individuals with a history of anaphylaxis caused by a non-food source such as wasp stings. The subjects' suitability for this study was determined by a comprehensive evaluation of allergic status, including a review of medical records and appropriate diagnostic tests.

A blood sample was collected from each subject and white blood cells removed. Genetic material (RNA) was extracted from collected white blood cells. A test was developed to investigate the region of interest within the RNA. RNA from each subject was tested twice, firstly to see if the normal genetic code was present within this region and secondly to detect the alteration seen previously in mastocytosis patients.

Fourteen of the 41 subjects were found to carry this alteration; they were not restricted to one group of volunteers but were spread throughout the four groups. There was a slight trend towards increased occurrence of the mutation in anaphylactic subjects but this was not found to be statistically significant.

It was concluded that the alteration was not found with sufficient frequency in individuals with severe allergies to be a useful marker of the risk of developing allergies. It was, however, unexpected to find this alteration present in normal healthy individuals and this suggests that this genetic alteration may not be limited to those with mastocytosis but may occur more frequently than previously thought in normal individuals.

The final report is available from the FSA Library and Information centre.
To obtain a copy, please contact the Enquiry Desk, Dr Elsie Widdowson Library and Information Services, Food Standards Agency (tel: 020 7276 8181/8182 or email: library&info@foodstandards.gsi.gov.uk)

Contact: For any enquiries concerning this research project, please contact the relevant Programme contact or email food.allergy@foodstandards.gsi.gov.uk