LIMITED POLYMORPHISM OF THE HLA-DQA2 PROMOTER AND IDENTIFICATION OF AVARIANT OCTAMER

Previous studies have suggested that the HLA-DQA2 gene may be associat ed with IDDM. The apparently limited allelism at this locus prompted u s to investigate whether this association might be with the level of g ene expression rather than with specific alleles. The proximal promote r region of HLA-DQA2 was sequenced in three homozygous DR4;DQ8 subject s with IDDM, six homozygous DR3;DQ2 subjects (three healthy controls a nd three with IDDM), and selected DR4 and DRG cell lines. This 388-bp region encompassed the known control W/Z/H/S, X, and Y boxes and inclu ded a previously unremarked variant octamer sequence 40 bp upstream of the transcription start site. Only one polymorphic site was present a mong these 15 sequences, found in one DR3;DQ2 subject and a DR6;DQ6 ce ll line. This indicates that any disease association with HLA-DQA2, at least among DR3;DQ2 individuals, cannot be accounted for solely by po lymorphism of the proximal promoter region.