A NEW MARKER IN THE HLA CLASS-I REGION IS ASSOCIATED WITH THE AGE AT ONSET OF IDDM

The (MHC) class II association with insulin-dependent diabetes mellitu s (IDDM) is well documented. However, it is likely that genes within t he MHC class III and the class I region also play a role in determinin g susceptibility to IDDM. In this study we have used a novel molecular probe to investigate the class I P3A and P3B loci of 179 patients wit h IDDM and 142 normal control subjects. A highly significant increase in the frequency of the class I P3 4.0;1.5 kilobase (kb) and 4.0;1.8;1 .5 kb genotypes was found in patients compared to the control subjects ((2)(chi) 46.8, 6 df, p < 0.0001). The association with the P3B 1.5 k b allele was strongly associated with the age at onset of diabetes, be ing present in 96.2% of subjects who developed diabetes between the ag e of 10-20 years compared to 55.0 and 74.6% who developed diabetes bef ore 10 years or after 20 years, respectively ((2)(chi) 31.4, p < 0.000 1). There was no evidence for linkage disequilibrium between the DQA1 and DQB1 loci and P3B suggesting that this is an independent associati on. In conclusion, these results suggest that genes in both the MHC cl ass I and II regions confer susceptibility to IDDM and are related to the age at onset of the disease.