MULTILOCUS ANALYSIS OF HLA CLASS-II GENES IN DR2-POSITIVE IDDM HAPLOTYPES IN FINLAND

gIn this study we characterized the haplotypes found in IDDM patients that normally confer resistance to the disease in order to localize th e polymorphisms relevant for the protection. We studied 15 DR2-positiv e subjects with IDDM for their DRB1, DRB5 and DQB1 genes using RFLP, p olymerase chain reaction (PCR), oligonucleotide typing, and in some sp ecific cases direct sequencing after allele-specific PCR. In addition we analyzed 39 DR2-positive, IDDM non-associated haplotypes representi ng those haplotypes that are not inherited to probands and hence are p resent only in healthy family members. The frequency of the DRB11501- DRB50101-DQB1*0602 haplotype was slightly decreased among diabetic pa tients (80% vs. 92%). In addition, two unconventional haplotypes DRB1 1501-DRB&0101-DQB1*05031 and DRB1*1501-DRB5*0101-DQB1*0502 were found in patients with IDDM while all the control ones were conventional. T he sequencing of the DQB10602 allele present in IDDM haplotypes showe d 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 DQA1 gene. All DR2-DQB10602 IDDM haplotypes were associated with the 2.1- kb fragment while in the control group the 2.1-kb and 1.9-kb fragments were evenly distributed.