GENETIC-HETEROGENEITY BETWEEN TYPE 1A AND TYPE 1B INSULIN-DEPENDENT DIABETES-MELLITUS - HLA CLASS-II AND TAP GENE ANALYSIS

The aim of this study was to compare the genetic susceptibility linked to the HLA Class II region genes of the Major Histocompatibility Comp lex in isolated insulin-dependent diabetes mellitus (1a-IDDM) and insu lin-dependent diabetes mellitus associated with another autoimmune end ocrinopathy (1b-IDDM). HLA genes DRB1, DQA1 and DQB1 were studied at t he genomic level, as well as genes TAP1 and TAP2. One hundred and seve nty-nine 1a-IDDM diabetic patients were compared with 83 1b-IDDM patie nts. While it appeared that common genetic traits characterize diabete s regardless of the subtype (1a or 1b), certain features differentiate the two forms of IDDM. Extending the analysis of risk haplotypes DRB1 03 and DRB1*04 to TAP genes elicited a difference between 1a-IDDM and 1b-IDDM patients. Haplotype DRB103 was thus characterized in 1a-IDDM patients by a lower frequency of alleles TAP1-B (13.5%) and TAP2-B (1 6.2%), not found in 1b-IDDM patients (33.3% for each allele). Likewise , haplotype DRB104 is characterized in 1b-IDDM patients by a lower fr equency of alleles TAP1-C (4.0%) and TAP2-B (8.0%) than in 1a-IDDM pat ients (22.2% and 25.9%, respectively). In total, this study showed tha t extending the characterization of HLA Class II haplotypes to TAP gen es discriminates between the forms of diabetes restricted to a specifi c pancreatic affection and those reflecting a wider autoimmune disorde r affecting several organs.