THE EFFECT OF HLA-B ALLELE ON THE IDDM RISK DEFINED BY DRB1-ASTERISK-04 SUBTYPES AND DQB1-ASTERISK-0302

The genes encoding the HLA-DQ heterodimer molecules, DQB1 and DQA1, ha ve been found to have the strongest association with IDDM risk, althou gh there is cumulative evidence for the effect of other gene loci with in the major histocompatibility complex gene region, After the HLA-DQ locus, the HLA-DR locus has been suggested most often as contributing to the disease susceptibility, In this study we analyzed at the popula tion level the effect of DR4 subtypes and class I, HLA-B alleles, on I DDM risk when the influence of the Do locus was stratified, In all thr ee populations studied (Estonian, Latvian, and Russian), DQB1-0302 hap lotypes most frequently carried DRB1-0401 or DRB1-0404, DRB1-0401 was the most prevalent subtype in IDDM patients, whereas DRB1-0404 was dec reased in frequency, DRB1-0402 was also prevalent among Russian haplot ypes, but was not associated with IDDM risk, When HLA-B alleles were a nalyzed, strong associations between the presence of specific B allele s and DRB1-04 subtypes were detected, The HLA-B39 allele was found sig nificantly more often in DRB1-0404-DQB1-0302-positive patients than in healthy control subjects positive for this haplotype: 27 of 54 (50%) vs, 4 of 49 (8.2%) (P < 0.0001), The results demonstrate that DQ and D R genes cannot explain all of the HLA-linked susceptibility to IDDM, a nd that the existence of a susceptibility locus telomeric to DR is pro bable.