Understanding the molecular basis of celiac disease: what genetic studies reveal

Ann Med. 2006;38(8):578-91. doi: 10.1080/07853890600989054.


Celiac disease (CD) is characterized by a chronic immune reaction in the small intestine to the gluten proteins that are present in a (Western) daily diet. Besides the well known involvement of the HLA class II histocompatibility antigen (HLA)-DQ2.5 and -DQ8 heterodimers (encoded by particular combinations of the HLA-DQA1 and -DQB1 gene) in CD and the minor contribution of the CTLA-4 gene, recently the myosin IXB (MYO9B) gene has also been found to be genetically associated. This review covers the general aspects of CD as well as current insight into important molecular aspects. We evaluate the role of susceptibility genes in CD by following gluten along its path from ingestion to uptake in the body, which leads us through the three aspects of CD's pathology. The first is the presence of gluten in the lumen of the intestine, where it is broken down by several enzymes. The second is the intestinal barrier through which gluten peptides pass. The third is the reaction of the immune system in response to gluten peptides, in which both the innate and the adaptive immune systems play a role. Our main conclusion, based on the current genetic and functional studies, is that we should look for causal genes in the barrier function as well as in the immune systems.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Celiac Disease / diagnosis
  • Celiac Disease / genetics*
  • Celiac Disease / immunology*
  • Glutens / metabolism
  • Humans
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Intestine, Small / immunology
  • Intestine, Small / metabolism


  • Glutens