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

There are large variations in the incidence of Type I (insulin-dependent) d iabetes mellitus within Europe, ranging from 3.2 cases per 100 000 person-y ears in the Republic of Macedonia to more than 40 new cases per 100 000 per son-years in Finland. This variation could be caused by differences in the distribution of genetic susceptibility markers, by differences in the distr ibution of environmental disease determinants or by a combination of both. To assess how much genes contribute to this variation, we correlated the le vel of incidence of Type I diabetes with the prevalence in the general popu lation of genetic susceptibility and protective markers encoded by the huma n leukocyte antigen (HLA)-DQ loci. Positive association was found for the c ombined 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 populat ion prevalence of genotypes not encoding for aspartate on position 57 on th e HLA-DQ beta chain. It was not possible to detect any negative correlation between Type I diabetes incidence and the prevalence of HLA-genotypes conf erring protection against Type I diabetes in a population (HLA-DQA1*0102-DQ B1*0602/X). The results suggest that a substantial part of the transnationa l variation in the incidence of childhood-onset Type I diabetes in Europe i s explained by variations between populations in the distribution of partic ular DQ genotypes which confer a high risk of Type I diabetes in the genera l population.