POLYMORPHISM OF ANTIGEN-PROCESSING (TAP, LMP) AND HLA CLASS-II GENES IN CELIAC-DISEASE

Susceptibility to CD is strongly associated with particular HLA class II molecules. However, additive genetic factors are likely to be requi red for the development of the disease. The polymorphic TAP and LMP ge nes, located within the HLA class II region, are involved in the antig en presentation pathway and thus represent candidate susceptibility ge nes. HLA class II DRB1, DRB3, DQA1, DQB1, and DPB1 as well as TAP1, TA P2, and LMP2 polymorphism was studied in 80 Caucasian CD patients and 213 normal controls by DNA oligotyping. The DQB10201 allele was found in 96.3% of CD patients and provided the highest risk (RR = 50), wher eas only 89% of CD patients carried the DQ alpha 501/beta 201 heterodi mer(RR = 30). The participation of the DRB3 and DPB 1 locus was ruled out as it was attributed to a linkage disequilibrium on the DR3 haplot ype. TAP1 and LMP2 allelic distribution was not significantly differen t among CD patients and controls. The TAP2-C allele was completely abs ent from the CD population, while it was found in 22.5% of controls. A lthough linkage disequilibrium between TAP2 and class II loci clearly exists in some haplotypes, TAP could act as additional susceptibility genes.