Immunogenetic, Clinical, and Demographic Characterization of Childhood Type I Diabetes in New Zealand

Abstract

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 9.6−14.3/100,000). 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 8.3 ± 5.1 years) than those with nonsusceptibility types (mean age 11.8 ± 4.7 years, P = 0.056). 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 and ICA at diagnosis, suggesting that variations at the DQB1 locus are not linked to the expression of this autoimmune marker of β-cell destruction.