Correlations between the incidence of childhood-onset Type I diabetes in Europe and HLA genotypes

Abstract

There are large variations in the incidence of Type I (insulin-dependent) diabetes mellitus within Europe, ranging from 3.2 cases per 100 000 person-years in the Republic of Macedonia to more than 40 new cases per 100 000 person-years in Finland. This variation could be caused by differences in the distribution of genetic susceptibility markers, by differences in the distribution of environmental disease determinants or by a combination of both. To assess how much genes contribute to this variation, we correlated the level of incidence of Type I diabetes with the prevalence in the general population of genetic susceptibility and protective markers encoded by the human leukocyte antigen (HLA)-DQ loci. Positive association was found for the combined group of genotypes associated with Type I diabetes risk (p < 0.001). The whole positive effect was, however, accounted for by the HLA-DQ2/DQ8 (DQA1*0501-DQB1*0201/DQA1*0301-DQ-B1*0302) and HLA-DQ4/DQ8 (DQA1*0401-DQB1*0402/DQA1*0301-DQB1*0302) genotypes (p < 0.001 and p < 0.004, respectively). No correlation was found between incidence of Type I diabetes and population prevalence of genotypes not encoding for aspartate on position 57 on the HLA-DQ β chain. It was not possible to detect any negative correlation between Type I diabetes incidence and the prevalence of HLA-genotypes conferring protection against Type I diabetes in a population (HLA-DQA1*0102-DQB1*0602/X). The results suggest that a substantial part of the transnational variation in the incidence of childhood-onset Type I diabetes in Europe is explained by variations between populations in the distribution of particular DQ genotypes which confer a high risk of Type I diabetes in the general population.