LINKAGE DISEQUILIBRIUM BETWEEN INSULIN-DEPENDENT DIABETES AND THE KIDD BLOOD GROUP Jkb ALLELE

We studied 102 randomly ascertained probands from the Upper Midwest United States with insulin-dependent diabetes mellitus (IDDM) with respect to both HLA-DR and Kidd (Jk) markers. Based on our evidence that multiple genetic mechanisms may be involved in the etiology of IDDM the data were partitioned according to the HLA-DR phenotype, containing either two high risk antigens (DR3 or DR4) or not. Probands with two such antigens showed no appreciable deviation from control frequencies, while the remainder displayed a slightly reduced relative risk for Jka (RR=0.70, p<25), but a significantly elevated risk for Jkb (RR=2.53, p<025). These results strongly suggest a complex model of IDDM inheritance involving, at least, one susceptibility locus in linkage disequilibrium with HLA DR3 and DR4 on chromosome 6, and a second locus in linkage disequilibrium with Jk3 on chromosome 2.