Summary Using a highly discriminatory DNA typing technique, based on the polymerase chain reaction and reverse dot blot hybridization, more refined results were obtained on the association of particular HLA class II alleles, haplotypes and genotypes with insulin-dependent diabetes mellitus in the Belgian population. The previously reported predisposing effect for the DRBI*0301 encoded DR3 serologic specificity was confirmed and could be assigned to the DRB3*0200 encoded DR52b serologic specificity. A second high risk haplotype, DRBI*0401-DQBI*0302 encoding the DR4-DQ8 serologic specificity, accounted for increased susceptibility both in the total insulin-dependent diabetic population and among DR4-positive patients. Moreover, we found that these DR4 associated DRB1 and DQB1 alleles act as independent risk factors. A possible role for the DPB1 locus can be rejected since the observed predisposing effect for DPBI*0202 probably occurred due to linkage disequilibrium of this allele with DRBI*0301. Particular extended haplotypes accounted for the decreased relative risk observed for the DR2, DR11 and DR13 serologic specificities. The highest relative risk was observed for those DQA1/DQB1 genotypes, allowing for the formation of 4SS (DQ0~Arg52+/DQflAsp57-) heterodimers. [Diabetologia (1994) 37: 808-817] Key words Insulin-dependent diabetes mellitus, HLA, class II, PCR, SSO typing.IDDM results from the autoimmune destruction of the pancreatic insulin-producing beta cells. Concordance rates for monozygotic twins (36 %), HLA-identical and -haplo-identical siblings (13 % and 4.5 %, respectively) suggest a multifactorial predisposition for this disease, the genetic factor being only partly determined by the HLA genes [1,2].

No abstract

SUMMARYPopulation and family studies show that predisposition to type I diabetes (IDDM) is multifactorial, and that polymorphisms in the MHC region contribute substantially to the susceptibility to IDDM. In the present study the association of polymorphisms in the CD4 and the 6 subunit of CD3 with IDDM were examined in a Belgian population. We observed that the frequency ofthe CD4*A4/A4 genotype and ofthe CD3*91 allele were significantly increased (i* = 00077) and decreased {P = 3'8 x 10"^), respectively, in IDDM compared with controls. These results therefore suggest that CD4, CD3 or neighbouring genes might contribute to IDDM susceptibility. These results are, however, preliminary and cannot be considered as established until re-tested in a population.

No abstract

Non‐insulin‐dependent diabetes mellitus has been recognized to be heterogeneous in etiology, with multiple subgroups. Several genes or chromosomal regions have been implicated in the development of the disease. In this study the association of HLA class II alleles and genotypes and the association of CD4 and CD3 polymorphisms were assessed in a large number of Belgian non‐insulin‐dependent diabetes mellitus patients. Furthermore, the importance of the DQα***Arg52/DQαlArg52 and the DQβlAsp57/DQβlAsp57 genotypes and the combination of both genotypes were examined. Our results show that in the HLA class II genes only the DQαlArg52+/DQαlArg52+ genotype was significantly associated with non‐insulin‐dependent diabetes mellitus compared with controls (p=0.011, RR=2.02). We also observed that the frequency of the CD4*A4/*A8 genotype and the CD4*A7 allele was significantly increased and decreased respectively in non‐insulin‐dependent diabetes mellitus patients as compared with the controls (p=0.018, RR=2.16 and p=0.0003, RR=0.49 respectively). These results therefore suggest that HLA class II and CD4 genes might independently contribute to the susceptibility for non‐insulin‐dependent diabetes mellitus and that these alleles and genotypes might identify subgroups of patients with different susceptibilities.