Asp57-negative HLA DQ beta chain and DQA1*0501 allele are essential for the onset of DQw2-positive and DQw2-negative coeliac disease.

The genetic predisposition to coeliac disease is associated with the HLA DQw2 allele. Coeliac patients lacking the DQw2 allele are very rare and always exhibit the DR4-DQw3 haplotype. We performed oligotyping of polymerase chain reaction (PCR)-amplified DQA1 and DQB1 genes in six DQw2-negative and 30 DQw2-positive coeliac patients. The DQB analysis showed that all six DQw2-negative patients possessed the DQB10302 allele. The other DQB alleles found in five of these patients were DQB10501, DQB10604 and DQB10302. The DQ beta chains encoded from all these alleles have the replacement of aspartic acid residue at position 57 (Asp57), as well as the DQB10201 allele which was found in all 30 DQw2-positive coeliac patients. The DQw2-negative proband who lacked the homozygous Asp57 replacement exhibited the DQA10501 allele in the DQA1 gene. The DQA10501 allele was also found in 27 of the 30 DQw2-positive coeliac patients. Among this group of coeliacs, the four cases lacking the DQA10501 allele exhibited the homozygous Asp57 replacement in the DQ beta chain. Our results indicate that Asp57-negative DQ beta alleles are involved in both DQw2-positive and -negative coeliac patients. Moreover, when the Asp57-negative DQ beta chain is encoded from only one of the two DQB1 genes the DQA1*0501 allele is always present.