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

Abstract

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).

Subtypes of HLA‐DQ and ‐DR defined by DQB1 and DRB1 RFLPs: allele frequencies in the general population and in insulin‐dependent diabetes (IDDM) and multiple sclerosis patients

“…The DR4.DQBl-band 8 haplotype, which corresponds to the DQw3.2 allele, was significantly increased in diabetics compared with controls ( P < 0.01). This association with a specific DQBl subtype of DR4 has been reported in previous population studies (Cohen et al 1984b;Todd et al 1987) and confirmed in an analysis of data from a large family study (Gogolin & Spielman, 1989). There were only two DR2-positive IDDM haplotypes among all IDDM individuals and both of these had the subtype that is less common among controls (DR2.DQBl-band 2).…”

Genetic analysis of IDDM: Summary of GAW5 IDDM results

“…In the two families segregating for both DQw alleles, only DQw3.2 is found in patients. Several participants Gogolin and Spielman, 1989) compared the frequency of DQw3.2 in "diabetic" compared to "control" parental HLA haplotypes defined as described above. The frequency of DQw3.2 was 0.94 (7540) among DR4-positive diabetic haplotypes, but only 0.67 (10115) among DR4-positive control haplotypes ( P < 0.005).…”