A DR3-related DX? gene polymorphism strongly associates with insulin-dependent diabetes mellitus

Abstract

HLA-DQ_α and HLA-DX_α gene polymorphisms were analyzed by Southern blot techniques in 78 Caucasoid insulin-dependent diabetes mellitus (IDDM) subjects and 55 control subjects. Five restriction fragment length polymorphisms of the HLA-DQ _α gene correlated with HLA-DR typing. Two allelic DX _α-related gene fragments, of 2.1 kb (U) and 1.9 kb (L) in size were identified. Genotype frequencies in the IDDM group for UU, UL, and LL were 54%, 38.5%, and 7.5%, respectively, whereas the corresponding frequencies in the control group were 24%,40%, and 36% (P < 0.00005 for differences in genotype frequencies). The U allele was associated particularly with IDDM patients who were DR3, with healthy controls who were DR3, as well as with IDDM patients who were not DR3. Thus, if this DX _α U allele is not the DR3-associated IDDM susceptibility gene, it is the closest marker hitherto studied.