Abstract:In this study we characterized the haplotypes found in IDDM patients that normally confer resistance to the disease in order to localize the polymorphisms relevant for the protection. We studied 15 DR2‐positive subjects with IDDM for their DRB1, DRB5 and DQB1 genes using RFLP, polymerase chain reaction (PCR), oligonucleotide typing, and in some specific cases direct sequencing after allele‐specific PCR. In addition we analyzed 39 DR2‐positive, IDDM non‐associated haplotypes representing those haplotypes that are not inherited to probands and hence are present only in healthy family members. The frequency of the DRB1*1501‐DRB5*0101‐DQB1*0602 haplotype was slightly decreased among diabetic patients (80% vs. 92%). In addition, two unconventional haplotypes DRB1*1501‐DRB5*0101‐DQB1*05031 and DRB1*1501‐DRB5*0101‐DQB1*0502 were found in patients with IDDM while all the control ones were conventional. The sequencing of the DQB1*0602 allele present in IDDM haplotypes showed no differences when compared to the controls. These results support the primary but not absolute role of DQ in the protection against IDDM. An additional role of factors centromeric to DQB1 gene was suggested by findings based on the biallelic TaqI RFLP polymorphism of the DQA2 gene. All DR2‐DQB1*0602 IDDM haplotypes were associated with the 2.1‐kb fragment while in the control group the 2.1‐kb and 1.9‐kb fragme