Analysis on allelic variation of the HLA‐DMB gene in Japanese by PCR‐RFLP as well as direct DNA sequencing and identification of a new DMB allele, DMB*0105

Abstract

In the HLA-D region, one of the class II genes, DMA and DMB have been identified between the DQ and DP genes, and four allelic polymorphisms in each of the DMA (DMA*0101 approximately 0104) and DMB (DMB*0101 approximately 0104) genes have been so far recognized. Several recent studies suggested that the DM molecule is required for class II antigen presentation pathway especially by promoting the binding of antigenic peptides to the classical HLA class II molecule. In this study, we have analyzed genetic polymorphism and allelic variation of the DMB gene in a Japanese population by the direct DNA sequencing technique and also by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, and could recognize DMB*0101 (49.3%), DMB*0102 (23.2%), DMB*0103 (23.2%), and DMB*0104 (0.4%). Further, a new DMB allele, DMB*0105 characterized by the presence of Val and Ile at two polymorphic sites, codons 144 and 179, respectively was identified. Strong linkage disequilibria were found between DMB*0101 and DRB1*0101, DPB1*0402 and DRB1*1502, and also between DMB*0103 and DRB1*1501 and DQB1*0602. HLA-DMB genotyping using the PCR-RFLP method established here will provide accurate evaluation of the effects of sequence allelism in the DMB gene on the HLA class II disease associations.