Distribution of HLA-DQA1^*01,^*03,^*05 and DQB1^*02 Subtypes and the Associated Haplotypes in the Korean Population

Abstract

IntroductionHLA-DQ proteins are encoded by the HLA-DQ genes and expressed as heterodimers of and chains at the cell surface (1-4). The HLA-DQ region consists of the matched genes (DQA1 and DQB1) and the pseudogenes (DQA2 and DQB2) (5,6). They are in linkage disequilibrium with the HLA-DR genes. Similarly to other HLA class II genes, the DQ genes show their polymorphic variation mainly in the second exon, which encodes the first extracellular domain of the molecule (5,7). However, distinct DQA1 alleles differ in exons other than the second exon. In particular, HLA-DQA1 0101, DQA1 0104, and DQA1 0105 alleles are distinguished in exons 1 and 4; identification of HLA-DQA1 0301, DQA1 0302, and DQA1 0303 alleles require typing of exons 1 and 3; and HLA-DQA1 0505 differs from DQA1 0501 alleles in exons 1 and 3 (8). Polymorphism at the HLA-DQB1 locus used to be determined by serology and recognized the specificities DQ1, DQ2, DQ3 and DQ4 (9). Subdivision of DQ1 and DQ3 resulted in the assignment of 5 additional serological DQB1 types, DQ5, DQ6, DQ7, DQ8 and DQ9 (10,11). The use of DNA typing techniques has increased the number of alleles. The allelic sequence diversity is also predominantly present in exon 2 and, except for DQB1 0201 and DQB1 0202, all alleles can be discriminated by PCR-SSOP in this exon. The nucleotide difference between DQB1 0201 and DQB1 0202 is located in exon 3 at codon 135 (12). The allele combination DQB1 0301/0302 and DQB1 0303/ 0304 yield an identical heterozygous sequence and there- ABSTRACTBackground: As all HLA class II genes, the DQ genes show their polymorphic variation mainly in the second exon, which encodes the first extracellular domain of the molecule. PCR-SSOP (Polymerase chain reaction-Sequence specific oligonucleotide probe) techniques were frequently used for HLA-DQA1 and DQB1 typing but certain alleles, DQA1 0101/0104/0105, 0302/0303, 0501/0505 and DQB1 0201/ 0202, which differ from each other in segment other than exon 2, could not be unequivocally assigned. Methods: To overcome this problem, we applied additional PCR-SSP (PCR-Sequence specific primer) method to analyze DQA1 exons 1, 3 and 4 and DQB1 exon 3. And we investigated the distributions and haplotypes of HLA-DRB1, DQA1 and DQB1 alleles in 406 unrelated Korean healthy individuals. Results: Using this method the indistinguishable alleles of DQA1 and DQB1 in PCR-SSOP were typed definitively. We also found several important associations between DQA1 and DQB1 alleles in the Korean population; DQA1 0101-DQB1 0501, DQA1 0104-DQB1 0502 or -0503, DQA1 0105-DQB1 0501, DQA1 0302-DQB1 0303, DQA1 0303-DQB1 0401 or -0402, DQA1 0501-DQB1 0201, DQA1 0505-DQB1 0301, and DQA1 0201-DQB1 0202. The haplotypes of DRB1-DQA1-DQB1 associated with DQA1 01, 03, 05, and DQB1 02 subtypes were investigated. Several haplotypes associated with these alleles were observed in the Korean population. Conclusion: Our results can be helpful to find potential unrelated donors for bone marrow registries and study the HLA-associated disease and anthropology ...