A GENE IN THE HLA CLASS-I REGION CONTRIBUTES TO SUSCEPTIBILITY TO IDDM IN THE FINNISH POPULATION

In Finland the haplotype A2, Cw1, B56, DR4, DQ8 is the third most comm on haplotype in insulin-dependent diabetic (IDDM) patients and has the highest haplotype-specific absolute risk for IDDM. Cw1, B56, DR4, DQ8 haplotypes containing HLA-A alleles other than A2 are infrequent in t he population and are not associated with IDDM. Comparison of the A2 a nd non-A2 haplotypes at the DNA level showed that they were identical at HLA-B, -DR, and -DQ loci. Evidence that class I alleles confer susc eptibility to IDDM was obtained from the two HLA-C, -B, -DR and -DQ ha plotypes most frequently found in IDDM patients in Finland. A24, A3 an d A2 on the Cw3, B62, DR4, DQ8 haplotype, and A28, A2 and A1 on the Cw 7, B8, DR3, DQ2 were all found to be associated with IDDM. In Finland these seven haplotypes, including A2, Cw1, B56, DR4, DQ8, account for 33 % of diabetic haplotypes and 10.3 % of non-diabetic haplotypes (p < 0.00001). The contribution of the class I region to IDDM susceptibili ty was also apparent in those IDDM patients lacking the disease-predis posing class II alleles. Significantly more non-DR3/non-DR4 IDDM patie nts (47 of 55) possessed two of the IDDM-associated HLA-A alleles comp ared to non-DR3/non-DR4 control subjects (40 of 58; p = 0.038). Moreov er, IDDM patients confirmed by oligotyping as unable to form a 'diabet es-susceptibility' DQ heterodimer, tended to possess two diabetes-asso ciated HLA-A alleles (12 of 13) compared to control subjects (12 of 20 ; p = 0.056).