Association of HLA-DQw3 (TA10⁻) With Type I Diabetes Occurs With DR3/4 but not DR1/4 Patients

We have shown in previous studies that the TA10⁻ subtype of HLA-DQw3 is significantly increased in HLA-DR4 type I (insulin-dependent) diabetic patients. Data presented in this article indicate that this association only occurs in heterozygous DR3/4 patients and not in DR1/4 patients. Because there is an interactive effect of both DR3/4 and DR1/4 in type I diabetes, the data indicate that the contribution of DR4 haplotypes varies depending on the haplotype borne on the homologous chromosome. In addition, the frequency of the B44-DR4 haplotype was shown to be decreased in DQw3 (TA10⁻) diabetic subjects who were DR3/4 compared with those who were DR1/4 or DR4/X (a pooled group of patients with different DR alleles). This finding suggests that the decrease in the B44-DR4 haplotype in type I diabetes is not solely dependent on its linkage disequilibrium with the DQw3 (TA10⁻) allele but suggests there is an additional effect exerted independently.