Led by David van Heel, Professor of Gastrointestinal Genetics at Queen Mary, University of London, the study - funded by the charity Coeliac UK, and the Wellcome Trust - has revealed that those suffering from coeliac disease lack a protective DNA sequence in a specific gene region, otherwise found in healthy individuals.
Behind the success of the study are the Human Genome Project and the Hap Map Project, international research efforts to reveal the entire sequence of all the human chromosomes - and the functional units embedded within - and to correlate that information to common sequence variation in the human population.
Dr Panos Deloukas, Senior Investigator in Human Genetics at the Wellcome Trust Sanger Institute, and part of the research consortium, said: “These resources coupled with technological advances have enabled us to scan variation across the human genome in large numbers of people for association to disease.” The Sanger Institute made available to the study the genome data on 1500 British individuals used as controls (i.e without coeliac disease). The consortium studied over four thousand individuals with and without coeliac disease, amongst British, Irish and Dutch populations.
What they found is that healthy individuals more often have a protective DNA sequence in the interleukin-2 and interleukin-21 gene region than individuals with coeliac disease. Interleukin-2 and interleukin-21 are cytokine proteins secreted by white blood cells that control inflammation. It is likely that the protective DNA sequence leads to different amounts of these cytokines being produced – than in someone with coeliac disease – providing defence against intestinal inflammation.
Coeliac disease is found in around 1 in 100 of the British population. It is caused by intolerance to gluten - a protein found in wheat, barley and rye - which results in damage to the gut, preventing normal digestion and absorption of food. If undetected it can lead to, amongst other things, anaemia, poor bone health, and weight loss. Although the majority of people are diagnosed in mid-life, symptoms can present themselves at anytime, for example during illness, stress, or post-trauma. There is a strong inherited (genetic) risk.
Professor David van Heel, chief investigator in the study, said; “We previously knew that coeliac individuals had a specific tissue type which recognised wheat proteins. We did not know why healthy individuals who had the same tissue type did not develop symptoms or disease. The first findings from our study suggest that interleukin genes that control inflammation are critical. We expect to find more disease risk factors from further in-depth analysis of the genome wide data.”
Sarah Sleet, Chief Executive of Coeliac UK said: ‘This research heralds an important breakthrough in understanding better who is likely to develop coeliac disease. Around 1 in 100 people develop the disease but predicting who is susceptible is like searching for a needle in a haystack. Currently genetic testing is a blunt instrument which can only narrow down the search to around one third of the general population’.
The study provides a road-map to enable discovery of further genetic risk factors predisposing to coeliac disease.
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