HLA DR4-DQw3.1 and 3.2 haplotypes among insulin-dependent diabetics and their unaffected sibs in the GAW5 data.

Almost all human leukocyte antigen (HLA) haplotypes positive for HLA-DR4 also carry the DQw3 specificity, which appears in one of two allelic forms, DQw3.1 or DQw3.2. Previous studies have shown that the frequency of the HLA DR4-DQw3.2 allele is approximately 95% among DR4-positive haplotypes of insulin-dependent diabetics (IDDM), but only 70% in DR4-positive haplotypes of unaffected individuals. Because this difference could be due to ethnic heterogeneity, it is important to establish whether the frequency of the DQw3.2 allele is also increased when haplotypes of diabetics are compared to those of "matched" unaffected individuals, as can be done within families. We have used the Genetic Analysis Workshop 5 (GAW5) data for this purpose. In every family, each parental DR4-bearing haplotype was categorized as "IDDM" if it appeared in any affected parent or offspring, or as "control" if not. When this was done, the frequencies of the DQw3.2 and 3.1 allele in 80 IDDM haplotypes were 94% and 6% respectively but 67% and 33% in 15 control haplotypes. This difference between the two kinds of haplotypes is highly significant (P less than 0.005).