On the HLA-DQ(alpha 1*0501, beta 1*0201)-associated susceptibility in celiac disease: a possible gene dosage effect of DQB1*0201.

The HLA-associated susceptibility to develop celiac disease (CD) seems mainly to be conferred by a particular HLA-DQ heterodimer encoded by the DQA10501 and DQB10201 genes either in cis or in trans position. To study the possible influence of DRB1 or other DQA1 and DQB1 alleles on the CD susceptibility conferred by these DQ genes, we performed genomic HLA typing of 94 CD patients, selected those who carried at least one copy of the DRB10301-DQA10501-DQB10201 haplotype (N = 89) and compared them to 47 random, healthy Norwegians matched with the patients to carry at least one copy of the above haplotype. We found an excess of DQB10201 homozygosity in the patients. This was due to an increased frequency of the DRB10301-DQA10501-DQB10201 and DRB10701-DQA10201-DQB10201 haplotypes present on the other chromosome. We propose that, in individuals carrying the DQA10501 and DQB10201 alleles, the presence of a second copy of the DQB1*0201 allele increases susceptibility to CD.