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: There is evidence that certain alleles at the HLA-DQ locus are correlated with susceptibility to insulin-dependent diabetes mellitus (IDDM) and in particular that DQ beta-chain alleles containing aspartic acid at position 57 are protective. The availability of a large group of patients with IDDM enabled us to assess the role of HLA-DQ alleles in susceptibility to the disease in order to confirm and extend recent observations derived from studies of smaller numbers of patients. Using allele-specific oligonucleotide probes and the polymerase chain reaction, we studied 266 unrelated patients with IDDM and 203 unrelated normal subjects for eight HLA-DQ beta-chain alleles.

Two major findings emerged from these studies. First, the presence of an HLA-DQw1.2 allele was protective. Only 6 of the 266 patients with IDDM (2.3 percent) were positive for HLA-DQw1.2, as compared with 74 of the 203 normal subjects (36.4 percent; P<0.001). Thus, persons with the HLA-DQw1.2 allele, which is one of the polymorphic forms of the beta chain of the HLA-DQ molecule, rarely had IDDM, no matter which other HLA-DQ beta-chain allele they inherited ("dominant protection"). Second, the presence of the HLA-DQw8 allele increased the risk of IDDM. The relative risk of IDDM was 5.6 in persons homozygous for HLA-DQw8, and it was similar in persons with the HLA-DQw1.1/DQw8 or HLA-DQw2/DQw8 haplotype ("dominant susceptibility"). However, the relative risk of IDDM in persons who had the HLA-DQw1.2/DQw8 haplotype was 0.37, demonstrating that the protective effect of HLA-DQw1.2 predominated over the effect of HLA-DQw8.

We conclude that the presence of the HLA Class II antigen DQw1.2 is strongly protective against the development of IDDM, and that complete HLA-DQ typing is necessary for accurate assessment of susceptibility to IDDM. (N Engl J Med 1990; 322:1836-41.)

: AMONG whites, the HLA-DR3 and HLA-DR4 alleles confer increased susceptibility to insulin-dependent diabetes mellitus (IDDM),1 2 3 4 5 6 but there is growing evidence that the alleles at the DQ rather than the DR locus are more intimately associated with this increased susceptibility.7 8 9 Both the HLA-DQ and the HLA-DR molecules are heterodimers made up of an alpha chain (34 kd) and a beta chain (29 kd). The chains are noncovalently associated, and both subunits are intrinsic membrane proteins. Most of the variability is found in the outer domains of these Class II molecules, and the regions of polymorphism are probably linked to disease susceptibility. [horizontal ellipsis]

Owned, published, and (C) copyrighted, 1990, by the MASSACHUSETTS MEDICAL SOCIETY