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.


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.
Vehik
Kendra
K
University of Colorado Denver, School of Medicine, Denver, Colorado, USA. kendra.vehik@uchsc.edu
Hamman
Richard F
RF
Lezotte
Dennis
D
Norris
Jill M
JM
Klingensmith
Georgeanna J
GJ
Rewers
Marian
M
Dabelea
Dana
D
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003120:Colorado / Q000453:epidemiology; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D005260:Female; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006630:Hispanic or Latino / Q000706:statistics & numerical data; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D012307:Risk Factors; D044465:White People
D006680:HLA Antigens; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II