title: 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-DQB1*0302) and HLA-DQ4/DQ8 (DQA1*0401-DQB1*0402/DQA*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-DQbeta 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.
authors.affiliation: Department of Population Health Sciences, National Institute of Public Health, Oslo, Norway.
authors.forename: K S
authors.initials: KS
authors.lastname: Rønningen
authors.forename: N
authors.initials: N
authors.lastname: Keiding
authors.forename: A
authors.initials: A
authors.lastname: Green
mesh_terms: D017668:Age of Onset; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology*; D005060:Europe / Q000453:epidemiology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics; D006801:Humans; D015994:Incidence; D008285:Major Histocompatibility Complex; D015995:Prevalence; D012044:Regression Analysis
chemical_list: D006680:HLA Antigens; D006683:HLA-DQ Antigens