The Tumour Necrosis Factor region in coeliac disease

Abstract

Coeliac disease is a disease of the small intestine, characterised by villous atrophy and crypt hyperplasia. The disease can be defined as an intolerance in genetically susceptible individuals to certain storage proteins such as gliadin found in wheat, barley and rye. In most cases the best treatment for patients is a gluten free diet. Coeliac disease can effect up to 1 in 132 individuals in Ireland. Symptoms of coeliac disease can include weight loss, vomiting, diarrhoea and abdominal bloating. The pathophysiology of gluten enteropathy is widely accepted as secondary to immunological mechanisms primarily related to T cell mediated events. Genetic susceptibility to coeliac disease is associated with the combination of the MHC HLADQA1*0501 and HLADQB1*0201 molecules which are coded for in the class II region of the HLA on chromosome 6. This combination has been found in 95% of coeliac patients. However, this is not the only susceptibility factor as a) approximately 30% of the normal population possess this allelic combination and do not have the disease and b) coeliac disease occurs in patients without this combination. The search for other HLA and non-HLA susceptibility genes has been intense. Genome scans have identified regions on 5q, 6p and 11q. However, replication of results in such studies has proved difficult. Candidate gene studies have also investigated the role of CTLA4 on chromosome 2 with conflicting results. Whereas, studies on the IL-lip gene on chromosome 5 found no association. The aim of this study was to investigate the role of the TNF region in susceptibility to coeliac disease.