Trends in high-risk HLA susceptibility genes among Colorado youth with type 1 diabetes.

OBJECTIVE

Type 1 diabetes is associated with a wide spectrum of susceptibility and protective genotypes within the HLA class II system. It has been reported that adults diagnosed with youth-onset type 1 diabetes more recently have been found to have fewer classical high-risk HLA class II genotypes than those diagnosed several decades ago. We hypothesized that such temporal trends in the distribution of HLA-DR, DQ genotypes would be evident, and perhaps even stronger, among 5- to 17-year-old Hispanic and non-Hispanic white (NHW) youth diagnosed with type 1 diabetes in Colorado between 1978 and 2004.

RESEARCH DESIGN AND METHODS

HLA-DR, DQ was typed using PCR and sequence-specific oligonucleotide hybridization in 100 youth diagnosed during the period of 1978-1988 and 264 diagnosed during 2002-2004. Logistic regression was used to adjust for confounders and assess temporal trends.

RESULTS

The frequency of the highest-risk genotype (DRB103-DQB102/DRB104-DQB103) was higher (39%) in children diagnosed during the period 1978-1988 than in those diagnosed during 2002-2004 (28%). A similar pattern was observed in NHWs and Hispanics.

CONCLUSIONS

We found that high-risk HLA genotypes are becoming less frequent over time in youth with type 1 diabetes of NHW and Hispanic origin. This temporal trend may suggest that increasing environmental exposure is now able to trigger type 1 diabetes in subjects who are less genetically susceptible.