ABSENCE OF PRIMARY ASSOCIATION BETWEEN DM GENE POLYMORPHISM AND INSULIN-DEPENDENT DIABETES-MELLITUS OR CELIAC-DISEASE

The DMA and DMB genes encode class II-like heterodimeric molecules loc ated in a specialized endocytic compartment, where they facilitate eff icient loading of antigenic peptides on HLA class II molecules. Both g enes are located within the MHC class II region and present a limited allelic polymorphism. Here we report the distribution of DM alleles in a group of 75 IDDM patients, 72 CD patients, and 162 random controls. We found a pronounced decreased frequency of DMA0102 in both patient groups relative to controls, This difference was, however, mainly sec ondary to a strong negative linkage disequilibrium (LD) between this a llele and the IDDM and CD-associated DRB103 allele. The DMB phenotype frequencies were similar in CD patients and controls. By contrast, we observed a decreased frequency of DMB0101 and an increased frequency of DMB0102 and DMB*0104 in IDDM patients, These differences disappea red when matching individuals for DRB103 or DRB1*04 alleles, which wa s in accordance with strong negative LD between DMB0101 and DRB1*04 o r DQB10302 alleles, and positive LD beta een DMB*0104 and DQB1*0201. Our data suggest that the apparent associations of IDDM or CD with giv en DM alleles are mostly secondary to primary associations with allele s at the DRB and DQB loci.