Trends in High-Risk HLA Susceptibility Genes Among Colorado Youth With Type 1 Diabetes
Published Date:Mar 20 2008
Source:Diabetes Care. 31(7):1392-1396.
Diabetes Mellitus, Type 1
European Continental Ancestry Group
Genetic Predisposition To Disease
Histocompatibility Antigens Class II
Polymerase Chain Reaction
Funding:00097/DP-05-069/DP/NCCDPHP CDC HHS/United States
432/CCU800 435-01/PHS HHS/United States
DK-32493/DK/NIDDK NIH HHS/United States
U01 DP000247/DP/NCCDPHP CDC HHS/United States
Description: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.|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.|The frequency of the highest-risk genotype (DRB1*03-DQB1*02/DRB1*04-DQB1*03) 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.|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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