The HLA-E locus is associated with age at onset and susceptibility to type 1 diabetes mellitus

Previous studies have suggested that the human leukocyte antigen (HLA) class I region may be involved in determining the age at onset and clinical severity of type 1 diabetes. We have investigated the frequency of polymorphisms of the nonclassical HLA class I gene, HLA-E, in 199 British Caucasian patients with type 1 diabetes and 82 healthy controls. A highly significant increase in the frequency of the HLA-E 0101 genotype was found in the patients compared to controls (chi(2) = 15.3, p < 0.00009). The frequency of the HLA-E 0101 genotype was increased in those patients diagnosed after 10 years of age, while the frequency of the 0101, 0103 genotype was significantly increased in those subjects diagnosed before 10 years of age (chi(2) = 26.0 p < 0.000003 and chi(2) = 13.0 p < 0.0003, respectively). No obvious interaction between the HLA-E locus and the class II DQB1*0201, 0302, and 0501 susceptibility alleles was found. This is the first report of an association between the HLA-E locus and susceptibility to an autoimmune disease.