SUSCEPTIBILITY TO TYPE-1 (INSULIN-DEPENDENT) DIABETES-MELLITUS IN SPANISH PATIENTS CORRELATES QUANTITATIVELY WITH EXPRESSION OF HLA-DQ-ALPHA ARG 52 AND HLA-DQ-BETA NON-ASP 57 ALLELES

HLA-DQ-alpha and beta-alleles were chosen as the most sensitive Type 1 (insulin-dependent) diabetes mellitus susceptibility markers for evaluating the disease associations and Type 1 diabetes risk in a population-based registry from Madrid. The absence of aspartic acid in position 57 of the DQ beta-chain (non-Asp 57), and the presence of arginine in position 52 of the DQ alpha-chain (Arg.52) were found to be reliable markers of Type 1 diabetes susceptibility among the Spanish population, with significantly higher frequencies among the cases of Type 1 diabetes compared to randomly selected non-diabetic control subjects from the general Madrid population. While non-Asp 57 homozygosity conferred an absolute risk of 32.3 per 100,000 per year and Arg 52 of 31.5 per 100,000 per year, the risk for double homozygotes for both non-Asp 57 and Arg 52 was estimated as 101.7 per 100,000 per year. Individuals homozygous for only one of these alleles, and heterozygous at the other locus, had a markedly lower Type 1 diabetes risk (12.8 per 100,000 per year), approximating the general population incidence for Madrid. Thus, susceptibility to Type 1 diabetes in Spanish patients is associated, quantitatively, with non-Asp 57 DQ-beta and Arg 52 DQ-alpha-alleles.