Celiac disease among Ashkenazi Jews from Israel. A study of the HLA class II alleles and their associations with disease susceptibility.

The immunogenetics of celiac disease demonstrates a highly significant association with the HLA class II alleles DQA10501 DQB10201 encoded in either a cis- or trans-configuration. In Northern Europe, these alleles are found in linkage disequilibrium with DRB10301 while in Southern Europe an additional secondary association through linkage disequilibrium is seen with the combination DRB11101/0701. This study examines 34 Ashkenazi Jews with celiac disease and 36 ethnically matched controls to determine alleles at the DRB, DQA1, DQB1, and DPB1 loci using SSO probes in conjunction with gene amplification by the PCR. The results confirm a highly significant association with the DQA10501 DQB10201 allelic combination (71% celiac vs 8% control individuals; p = 0.00005; chi 2 = 21.4). Of celiac subjects, 29% were negative for the proposed DQ susceptibility alleles, the majority of whom were DRB10402 positive (20% overall celiac group). No additional susceptibility was associated at the DRB3 and DPB loci. This study confirms that the MHC-linked celiac disease susceptibility among Ashkenazi Jews is closely associated with the presence of the combination of alleles DQA10501 DQB1*0201. However, within this population of relatively high-prevalence celiac disease, 30% of celiac patients do not carry these alleles and are therefore not covered by a single "unifying" hypothesis.