Immunogenetic, clinical, and demographic characterization of childhood type I diabetes in New Zealand

OBJECTIVE - To examine the relationship between genetic susceptibility alleles and islet cell antibodies (ICAs) in type I diabetes. RESEARCH DESIGN AND METHODS - The human leukocyte antigen (HLA)-DQB1 alleles and ICA levels of all incident type I diabetic cases in patients <20 years of age diagnosed in 1990 and 1991 in Canterbury, New Zealand, were determined. RESULTS - The mean annual incidence rate for type I diabetes over the 24 months was 19.0/100,000 patient years (95% confidence interval [CI] 13.5-26 0/100,000), which was considerably higher than rates observed between 1982 and 1989 (11.7/100,000; 95% CI 96-14. 3/100,000) ICAs ≥10 Juvenile Diabetes Foundation units (JDF U) were present in 84.6% of the subjects, but there was a higher prevalence of ICA-negative (ICA^-) subjects among those diagnosed during the winter months. The frequencies of the susceptibility allele DQB1*0302 and susceptibility genotype 0302/0201 were 71.8% and 43.5%, respectively. Subjects with 0302 tended to be younger (mean age 803 ± 5.1 years) than those with nonsusceptibility types (mean age 11.8 ± 4.7 years, P = 0056). The probability of being ICA positive (ICA⁺) was not significantly different between subjects with allele 0302 (85.7%) and those without it (81.8%). All seven patients negative for ICA were homozygous for DQB1 nonaspartate-57. There was no clustering of the immunogenetic markers with demographic and clinical characteristics apart from age at diagnosis CONCLUSIONS - No direct relationship was observed between DQB1-defined genetic susceptibility anti ICA at diagnosis, suggesting that variations at the DQB1 locus are not linked to the expression of this autoimmune marker of β-cell destruction.