GENETIC-STRUCTURE OF IDDM1 - 2 SEPARATE REGIONS IN THE MAJOR HISTOCOMPATIBILITY COMPLEX CONTRIBUTE TO SUSCEPTIBILITY OR PROTECTION

We analyzed 11 markers in the IDDM1 region in 120 IDDM patients and 83 healthy control subjects who were fully matched for the highest risk HLA-DQA10301-DQB1*0302/DQA1*0501-DQB1*0201 genotype, Our study provid es strong evidence that two regions in the major histocompatibility co mplex contribute to IDDM susceptibility or protection. First, despite selection for highest IDDM-associated risk DQ genotypes, this region d isplays extensive linkage disequilibrium (LD) differences between IDDM patients and control subjects, A second critical region was mapped ar ound the microsatellite locus D6S273 centromeric of TNF, and it is sim ilar to 200 kb in size, LD analysis shows that ''diabetogenic haplotyp es'' may have resulted from a recombination telomeric of D6S1014 in th e region of D6S273 and TNFa, Haplotype analysis using HLA and microsat ellite loci refines IDDM risk assessment in carriers of the HLA-DQ hig hest risk genotype.