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Recent advances in coeliac disease genetics
  1. Karen A Hunt,
  2. David A van Heel
  1. Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, London, UK
  1. Dr K A Hunt, Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, 4 Newark St, Whitechapel, London E1 2AT, UK; k.a.hunt{at}

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Around 1 in 100 individuals of European descent have coeliac disease. An immune response in the small intestine is generated to fragments of “gluten”, storage proteins found in wheat, rye and barley. The inflammatory response leads to architectural changes in the small intestine, including villous atrophy, crypt hyperplasia and an increase in the number of intra-epithelial cells. If gluten is removed from the diet, in many cases architecture returns to normal over several months. While gluten is one well known environmental factor, inherited genetic factors are also know to affect disease susceptibility as can be seen from twin and family studies.1 Identification of these genetic factors has been advanced substantially by the first genome-wide association scan (GWAS) in coeliac disease.2 This, along with a follow-up study, has identified eight new genomic regions, seven of which contains genes with immunological functions.2 3


Until recently the only well replicated genetic association for coeliac disease was with variants in the human leucocyte antigen (HLA) region. These molecules are encoded at chromosome 6p21 in the major histocompatibility complex (MHC) region which encodes over 200 genes with immunological function.4 MHC class II molecules are encoded at gene loci HLA-DQ, HLA-DP and HLA-DR, and are expressed on professional antigen presenting cells (APCs). The function of these molecules is to present exogenous antigen to T cells.46 These genes are highly polymorphic resulting in the presence of many different forms such as HLA-DQ2. Ninety per cent of patients with coeliac disease express HLA-DQ2 (DNA encoded by alleles DQA1*0501 and DQB1*0201), compared to 30% of the healthy population.7

Linkage studies have been highly successful in the search for susceptibility loci in monogenic disorders but this success has not carried over into complex diseases which are thought to arise due …

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