HLA-DRB4 GENOTYPING BY PCR-RFLP - DIVERSITY IN THE ASSOCIATIONS BETWEEN HLA-DRB4 AND DRB1 ALLELES

The serologically defined HLA-DR53 antigen is associated with HLA-DR4, -DR7, and -DR9 antigens, and these haplotypes contain two functional genes, DRB1 and DRB4, and two pseudogenes, DRB7 and DRB8. The DRB4 gen e encodes the DR53 antigen, and has been officially recognized to cont ain three allelic variants (DRB40101, 0102, and 0103). In this study, we have established the polymerase chain reaction - restriction fragm ent length polymorphism (PCR-RFLP) method for DRB4 genotyping and anal yzed genetic polymorphism of the DRB4 gene in Japanese population. DRB 40101, DRB4*0102, and DRB4*0103 could be observed at the frequencies of 0.5%, 1.1% and 32.7%, respectively. The same DRB1 allele does not n ecessarily share an identical DRB4 allele. Further, a tight linkage di sequilibrium was found between DRB40102 and DRB1*0401 in Japanese pop ulation, whereas DRB10401 was associated with DRB4*0101 or *0103 in C aucasian population. These findings reveal extensive diversity of the HLA-DRB1 and -DRB4 haplotypes and may have important implications for HLA-disease associations and donor selection in unrelated transplantat ion.