HLA-LINKED GENES ACTING AS ADDITIVE SUSCEPTIBILITY FACTORS IN CELIAC-DISEASE

Susceptibility to developing CD is widely accepted to be primarily ass ociated with a particular HLA-DQ alpha beta heterodimer encoded by the DQA1()0501 and DQB1(*)0201 alleles in cis position on the DR3,DQ2 ha plotype or in trans position by DR5,DQ7/DR7,DQ2 heterozygotes. We perf ormed genomic HLA-DR and DQ typing of 100 unrelated Spanish celiac chi ldren and 180 ethnically matched controls. As expected, most (92 out o f 100) celiac patients carried the HLA-DQ alpha beta heterodimer, and we selected these individuals for further studies. The results corrobo rate that although the DQA1()0501 and DQB1(*)0201 genes in single dos age appear sufficient for conferring disease susceptibility, individua ls homozygotes for DQB1()0201 show an increased risk. Furthermore, ou r data also show that those carrying the genotype DR5,DQ7/DR7,DQ2 have a significantly increased risk of developing CD as compared to those that are non-DR7 positive, also carrying the CD-associated HLA-DQ alph a beta heterodimer. This strongly suggests that there is an MHC linked non-HLA-DQ gene primarily associated with CD present on DR7,DQ2 haplo type, which should either be DR7 or in strong linkage disequilibrium w ith it. Our data also indicate that, as has already been suggested, an other HLA-associated CD susceptibility gene may be present on some DR4 -carrying haplotypes.