Abstract

Objective Type 1 diabetes is associated with a wide spectrum of susceptibility and protective genotypes within the Human Leukocyte Antigen (HLA) Class II system. It has been reported that adults diagnosed with youth-onset type 1 diabetes more recently 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 5-17 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 the polymerase chain reaction (PCR) and sequence-specific oligonucleotides (SSO) hybridization in 100 youth diagnosed during 1978-88 and 264 diagnosed in 2002-04. Logistic regression was used to adjust for confounders and assess temporal trends.

Results The frequency of the highest-risk genotype (DRB1*03-DQB1*02/DRB1*04-DQB1*03) was higher (39%) in children diagnosed in 1978-88 compared to those diagnosed in 2002-04 (28%). A similar pattern was observed in NHW 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.