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 HLADQA1*O3O1-DQB1*O3O2/DQA1*O5O1-DQB1*O2O1 genotype. Our study provides strong evidence that two regions in the major histocompatibility complex contribute to IDDM susceptibility or protection. First, despite selection for highest IDDM-associated risk DQ genotypes, this region displays extensive linkage disequilibrium (LD) differences between IDDM patients and control subjects. A second critical region was mapped around the microsatellite locus D6S273 centromeric of TNF, and it is ∼200 kb in size. LD analysis shows that “diabetogenic haplotypes” may have resulted from a recombination telomeric of D6S1014 in the region of D6S273 and TNFa. Haplotype analysis using HLA and microsatellite loci refines IDDM risk assessment in carriers of the HLA-DQ highest risk genotype.
Genetic Structure of IDDM1: Two Separate Regions in the Major Histocompatibility Complex Contribute to Susceptibility or Protection
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P Hanifi Moghaddam, P de Knijf, B O Roep, B Van der Auwera, A Naipal, F Gorus, F Schuit, M J Giphart, Belgian Diabetes Registry; Genetic Structure of IDDM1: Two Separate Regions in the Major Histocompatibility Complex Contribute to Susceptibility or Protection. Diabetes 1 February 1998; 47 (2): 263–269. https://doi.org/10.2337/diab.47.2.263
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