title: Asp57-negative HLA DQ beta chain and DQA1*0501 allele are essential for the onset of DQw2-positive and DQw2-negative coeliac disease.
abstract: 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 DQB1*0302 allele. The other DQB alleles found in five of these patients were DQB1*0501, DQB1*0604 and DQB1*0302. The DQ beta chains encoded from all these alleles have the replacement of aspartic acid residue at position 57 (Asp57), as well as the DQB1*0201 allele which was found in all 30 DQw2-positive coeliac patients. The DQw2-negative proband who lacked the homozygous Asp57 replacement exhibited the DQA1*0501 allele in the DQA1 gene. The DQA1*0501 allele was also found in 27 of the 30 DQw2-positive coeliac patients. Among this group of coeliacs, the four cases lacking the DQA1*0501 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.
authors.affiliation: Tissue Typing Laboratory, Malpighi Hospital, Bologna, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Mantovani
authors.forename: G R
authors.initials: GR
authors.lastname: Corazza
authors.forename: M
authors.initials: M
authors.lastname: Bragliani
authors.forename: M
authors.initials: M
authors.lastname: Frisoni
authors.forename: M G
authors.initials: MG
authors.lastname: Zaniboni
authors.forename: G
authors.initials: G
authors.lastname: Gasbarrini
mesh_terms: D000483:Alleles; D001224:Aspartic Acid / Q000032:analysis*; D002446:Celiac Disease / Q000235:genetics* / Q000276:immunology; D006683:HLA-DQ Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006801:Humans; D011110:Polymorphism, Genetic
chemical_list: D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C053186:HLA-DQ2 antigen; C069050:HLA-DQA1 antigen; C057615:HLA-DQbeta antigen; D001224:Aspartic Acid