HLA CLASS-II AND SUSCEPTIBILITY AND RESISTANCE TO INSULIN-DEPENDENT DIABETES-MELLITUS IN A POPULATION FROM THE NORTHWEST OF SPAIN

The role of HLA class II alleles in genetic predisposition to insulin- dependent diabetes mellitus (IDDM) was examined using Polymerase Chain Reaction/oligonucleotide probe typing (PCR/SSOs) of eight HLA class I I loci in 58 IDDM patients and 50 healthy controls from the Northwest of Spain (Asturias). We compared the distribution of HLA class II alle les, haplotypes and genotypes between IDDM patients and controls, and tested three recently proposed HLA-IDDM susceptibility theories. By us ing the aetiologic fraction (delta) as an almost absolute measure of t he strongest linkage of disequilibrium of a HLA marker to the putative Type I susceptibility locus. it has been found that the strength of a ssociation of the HLA markers may be quantified as follows: DQA103-DQ B10302 or DQA1*0501-DQB1*0201 > DR3 or DR4; presence of more than one dimer DQ alpha beta of the six proposed by Ronningen > non-Asp57 DQ b eta and Arg52 DQ alpha > Arg52 DQ alpha > non-Asp57 DQ beta/non-Asp57 DQ beta > DRB10301; DQA1*0501-DQB1*0201 > DQA1*03-DQB1*0302; DQB1*030 2. The presence of at least one Asp57 DQ beta allele was the best prot ection HLA market to IDDM in our population. Therefore, the above data confirm that IDDM susceptibility to HLA locus is linked more to DQ th an DR.