Human leukocyte antigen non-class II determinants for type 1 diabetes in the Finnish population.

We explored the contribution of non-class II HLA loci to type 1 diabetes genetic susceptibility in the Finnish population. We analyzed 11 markers covering a 4-Mb region telomeric to the DQB1 gene in Finnish nuclear families with parents carrying either the DR8-DQB104 (n=188) or the DRB10404-DQB10302 haplotypes (n=135). On the DRB10404-DQB10302 haplotype we found independent disease association of the D6S273 and C125 markers (p(corr) = 10(-4) and 0.0095, respectively). The C125200 alleles on this haplotype conferred an increased disease risk (OR = 3.6; p = 0.003). The B39 allele also showed disease association (OR = 2.6; p = 0.054). The C125200 allele appeared at an increased frequency also on transmitted B39 positive DRB10404-DQB10302 haplotypes, suggesting an independent effect. In addition, the C143417 allele on the DRB108-DQB104 haplotype was associated with decreased disease risk (OR = 0.48, p = 0.003). Our data confirm that non-class II HLA loci affect genetic susceptibility to type 1 diabetes. In addition to HLA B39 the C125 locus contributes to disease risk on the Finnish DRB10404-DQB10302 haplotypes. Another locus close to D6S273 may also have an effect. For the first time we report that a locus near the C143 marker appear to affect disease association of the DRB108-DQB104 haplotype.