GENETIC SUSCEPTIBILITY MARKERS IN DANISH PATIENTS WITH TYPE-1 (INSULIN-DEPENDENT) DIABETES - EVIDENCE FOR POLYGENECITY IN MAN

Fifty-five Danish families with two offspring concordant for type 1 di abetes - identified through a nationwide population-based survey, and 57 ''true sporadic'' cases - matched with familial cases for age at on set, but with no IDDM-affected first-degree relatives and long disease duration, and 110 control subjects were typed for putative genetic su sceptibility markers for type 1 diabetes identified from a pathogeneti c model. The markers included MHC class I, II and III loci, the mangan ese superoxide dismutase (MnSOD) locus (chr. 6q), interleukin-1 beta ( IL1B), the IL-1 receptor antagonist (IL1RN), and the IL-1 type 1 recep tor (IL1RI) loci (each chr. 2q). No significant differences between fa milial and sporadic cases were found within the MHC region (including the following loci: HLA-DQ, -DR, heat shock protein (HSP) 70, tumour n ecrosis factor (TNF), HLA-B and -A). In both groups of patients 11% we re negative for both DQA1()0301-DQB1(*)0302 and DQA1(*)0501-DQB1(*)02 01 genotypes, and 7% of the type 1 diabetics had genotypes unable to e ncode a susceptibility DQ alpha beta heterodimer. Disease association was found for the IL1RN (p = 0.04) and for the IL1RI (p = 0.03). When comparing controls and only familial cases with type 1 diabetes for th e IL1RN polymorphism a difference was observed (p = 0.003). For the IL 1B RFLP a trend for difference was observed between familial cases and control subjects (p = 0.046), whereas no differences between sporadic cases and control subjects could be demonstrated neither at the IL1B nor at the IL1RN loci. A difference in the MnSOD pattern was observed between sporadic cases and controls (p = 0.04).