**2.3 Genetic factors**

The importance of a genetic component for the development of CD is evident, based on the familial occurrence and the high concordance among identical twins [23, 24]. Almost 100% of patients with CD possess specific variants of the HLA class II genes HLA-DQA1 and HLA-DQB1 that, together, encode the two chains (α and β) of CD-associated heterodimer proteins DQ2 and DQ8 that are expressed on the surface of antigen-presenting cells [25]. More than 90% of patients with CD are DQ2 positive and most of the others are DQ8 positive [26]. HLA-DQ2 and HLA-DQ8 risk heterodimers are present in approximately 30–40% of the general population, and of these, approximately 1% develop the disease, so HLA DQ2/8 seems necessary, but not sufficient for the development of CD [27].

Several studies have been carried out to identify non-HLA susceptibility genes. Among these are a large number of CD-associated genes basically encode interleukins, interleukin receptors, and tumor necrosis factors or receptors that are involved in innate immunity and epithelial stress signals (COELIAC2, COELIAC 3, CTLA4, and COELIAC4) [28].
