Non-class IIHLA gene associated with type 1 diabetes maps to the 240-kb region near HLA-B

Several studies provide evidence that in addition to the DQ-DR genes, HLA c ontains another uncharacterized gene pr genes associated with type 1 diabet es. Our aim was to investigate the effect of this gene independently of the DQ-DR genes' and to localize it with a matched case-control study. More th an 1,400 patients and 30,000 control individuals from Finland were studied. They mere first genotyped for the selected alleles of the HLA-DQB1, -DQA1, and -DRB1 genes. For the DR3/4(0404) genotype, 75 patients and 181 control subjects were stratified, and 241 patients and 354 controls were stratifie d for the DR3/4(0401) genotype. Ten microsatellite markers in the HLA class III and I regions (D6S273, TNFa, C12A, STR MICA, MIB, C125, C143, C245, C3 211, and MOGc) and selected alleles of the HLA-A and HLA-B genes were studi ed. In the DR3/4(0404)-stratified group, we found that markers located betw een C12A and C143 near the HLA-B gene confer a strong additional diabetes a ssociation. This was confirmed by the population differentiation test in bo th DR3/4(0404)- and DR3/4(0401)-stratified groups. Our data indicate that a n additional gene associated with type 1 diabetes is located in the 240-kb region near HLA-B. We excluded STR MICA polymorphism as a mutation responsi ble for diabetes association.