The influence of polymorphism in the HLA-DQα1 and HLA-DQβ1 alleles on the age of onset of insulin dependent diabetes mellitus

Abstract

The objective of this investigation was to determine whether polymorphism in the HL-DQα and HLA-DQβ1 alleles, and the combination of different alleles, is related to the age of onset and susceptibility to IDDM. Patients from Canterbury, New Zealand, diagnosed with IDDM between 1990 and 1996, were used for analysis. Of the 142 subjects in the trial, 20 were non diabetic controls from the Canterbury region, 16 were over the age of 25 at diagnosis of IDDM, and the remaining 106 were individuals who developed IDDM under the age of 20. The entire trial group was HL-DQα1 typed using PCR followed by hybridisation techniques. As a result of complications and time constraints, only 2 subjects were HLA-DQβ1 typed by PCR amplification, restriction digestion and visualisation by gel electrophoresis. HLA-DQα1 0102 and 0201 alleles were significantly higher in the controls compared to IDDM patients (p<0.0020 and p<0.0003 respectively). The HLA-DQα1 allele 0301 was significantly higher in IDDM patients compared to controls (p<0.03). Comparison of age of onset of IDDM showed that the 0102 allele was significantly lower in subjects diagnosed with IDDM at <20 years of age compared to the 25+ age group (p<0.02). The allele combinations 0102, 0401/0501/0601 and 0103, 0401/0501/0601 were significantly higher in the 25+ IDDM subjects compared to those <20 years (p<0.005 and p<0.001 respectively). The 0301, 0401/0501/0601 allele combination was higher in IDDM patients <10 years of age compared to 25+ years of age (p<0.05). <10 years of age compared to 25+ years of age (p<0.05).