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 DQB1*0201 encoded in either a cis- or trans-configuration. In Northern Europe, these al leles are found in linkage disequilibrium with DRB 10301 while in Sou thern Europe an additional secondary association through linkage diseq uilibrium is seen with the combination DRB11101/0701. This study exam ines 34 Ashkenazi Jews with celiac disease and 36 ethnically matched c ontrols to determine alleles at the DRB, DQA1, DQB1, and DPB1 loci usi ng SSO probes in conjunction with gene amplification by the PCR. The r esults confirm a highly significant association with the DQA10501 DQB 10201 allelic combination (71% celiac vs 8% control individuals; P = 0.00005; X(2) = 21.4). Of celiac subjects, 29% were negative for the p roposed 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 D QB10201. However, within this population of relatively high-prevalenc e celiac disease, 30% of celiac patients do not carry these alleles an d are therefore not coveted by a single ''unifying'' hypothesis.