DQA1*03 subtypes have different associations with DRB1 and DQB1 alleles.

Polymorphisms outside the hypervariable regions of HLA class II alleles that do not affect the peptide-binding site are probably not under selective pressure and could therefore be useful as markers of the evolutionary pathways of the HLA class II haplotypes. We have analyzed such a polymorphism in the variants of DQA103, which differ at residue 160 encoded in exon 3. Our study included homozygous BCLs of the 10th IHWS and samples of a multiracial panel of 723 unrelated subjects which were also typed for allelic variations in exon 2 by hybridization with SSOP. BCLs having DQA103 and 131 selected DQA103-positive samples were typed for the dimorphism in exon 3 that distinguishes DQA10301 and DQA10302. DQA10301 was found to be exclusively associated with DQB10302, while samples carrying DQB10201, 0301, 0303, and 0401 always had DQA10302. A few haplotypes carrying DQB10302 had DQA10302. The fact that DQA10301 is completely included in DQB10302, and not vice versa, suggests that DQA10301 may have arisen from a mutation in a haplotype containing DQA10302-DQB10302. DQB10302 was found to be associated with all DR4 subtypes, suggesting possibly that the current variants of DRB1-DR4 may be of more recent origin. DRB10405 was the only subtype of DR4 which was not associated with DQA1*0301 and had multiple associations with the DQB1 alleles, therefore, perhaps representing the oldest allele of this group.