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

Diabetes Care. 2008 Jul;31(7):1392-6. doi: 10.2337/dc07-2210. Epub 2008 Mar 20.


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 (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.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Colorado / epidemiology
  • Diabetes Mellitus, Type 1 / epidemiology
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / immunology*
  • Female
  • Genetic Carrier Screening
  • Genetic Predisposition to Disease*
  • HLA Antigens / genetics*
  • HLA-DQ Antigens / genetics
  • HLA-DQ beta-Chains
  • HLA-DR Antigens / genetics
  • HLA-DRB1 Chains
  • Hispanic or Latino / statistics & numerical data
  • Histocompatibility Antigens Class II / genetics
  • Humans
  • Male
  • Polymerase Chain Reaction
  • Risk Factors
  • White People


  • HLA Antigens
  • HLA-DQ Antigens
  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • Histocompatibility Antigens Class II