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Diabetes Care Publish Ahead of Print published online ahead of print March 20, 2008
DOI: 10.2337/dc07-2210
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Original Research

Trends in High-Risk HLA Susceptibility Genes Among Colorado Youth with Type 1 Diabetes

Kendra Vehik, MPH, PhD1, Richard F. Hamman, MD, DrPH1, Dennis Lezotte, PhD1, Jill M. Norris, MPH, PhD1, Georgeanna J. Klingensmith, MD1,,2, Marian Rewers, MD, PhD1,,2 and Dana Dabelea, MD, PhD1

1University of Colorado Denver, School of Medicine, Denver, CO
2Barbara Davis Center, Aurora, CO

kendra.vehik{at}uchsc.edu

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.


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