HLA-Associated Phenotypes in Youth with Autoimmune Diabetes
Published Date:Aug 23 2012
Source:Pediatr Diabetes. 14(2):121-128.
African Continental Ancestry Group
Diabetes Mellitus, Type 1
European Continental Ancestry Group
Genetic Predisposition To Disease
Type 1 Diabetes
Pubmed Central ID:PMC3932799
Funding:1U18DP002709/DP/NCCDPHP CDC HHS/United States
1UL1RR026314-01/RR/NCRR NIH HHS/United States
DP-05-069/DP/NCCDPHP CDC HHS/United States
M01 RR00069/RR/NCRR NIH HHS/United States
M01RR00037/RR/NCRR NIH HHS/United States
P30 DK57516/DK/NIDDK NIH HHS/United States
U01 DP000244/DP/NCCDPHP CDC HHS/United States
U01 DP000247/DP/NCCDPHP CDC HHS/United States
U01 DP000248/DP/NCCDPHP CDC HHS/United States
U01 DP000250/DP/NCCDPHP CDC HHS/United States
U01 DP000254/DP/NCCDPHP CDC HHS/United States
U01DP000245/DP/NCCDPHP CDC HHS/United States
U01DP000246/DP/NCCDPHP CDC HHS/United States
U18DP000247-06A1/DP/NCCDPHP CDC HHS/United States
U18DP002708-01/DP/NCCDPHP CDC HHS/United States
U18DP002710-01/DP/NCCDPHP CDC HHS/United States
U18DP002714/DP/NCCDPHP CDC HHS/United States
U48/CCU419249/PHS HHS/United States
U48/CCU519239/PHS HHS/United States
U48/CCU819241-3/PHS HHS/United States
U48/CCU919219/PHS HHS/United States
U58/CCU019235-4/PHS HHS/United States
U58CCU919256/PHS HHS/United States
UL1 RR025014/RR/NCRR NIH HHS/United States
UL1 TR000077/TR/NCATS NIH HHS/United States
UL1 TR000423/TR/NCATS NIH HHS/United States
UL1RR029882/RR/NCRR NIH HHS/United States
To examine HLA DRB1-DQB1 haplotypes within a multi-ethnic cohort and assess their association with characteristics of diabetes onset.
The sample included 1,662 participants from the SEARCH for Diabetes in Youth Study who tested positive for GADA and/or IA-2A autoantibodies. Blood drawn at the study visit was used to measure fasting C-peptide and genotype HLA DRB1 and DQB1 loci. Diabetic ketoacidosis (DKA) at diagnosis was determined from medical records. Multivariable linear and logistic regression models stratified by race/ethnicity were used to assess associations with DRB1-DQB1 haplotypes.
The frequency of DRB1*03 susceptibility haplotypes ranged 27.5–28.9% in all racial/ethnic groups. The frequency of susceptibility DRB1*04-DQB1*0302 was higher in non-Hispanic white (NHW; 34.1%) and Hispanic (38.9%) compared to non-Hispanic black (NHB; 20.8%) youth. Neutral and protective haplotypes were low frequency in all groups. DBR1*03 haplotypes were associated with younger age at diagnosis in NHW and positivity for multiple autoantibodies in Hispanics. DRB1*04-DQB1*0302 haplotypes were associated with multiple autoantibody positivity in NHW and Hispanics, and lower fasting C-peptide and higher odds of DKA in Hispanics only. Although protective DRB1*04-DQB1*0301 haplotypes were associated with older age at diagnosis in NHW, they were also associated with multiple autoantibody positivity in these youth. Protective DRB1*13 haplotypes were associated with decreased odds of multiple autoantibody positivity in NHB youth.
The distribution of DRB1-DQB1 haplotypes and their association with onset-related characteristics of autoimmune diabetes varies across major racial/ethnic groups in the United States. This may contribute to variation in clinical presentation of autoimmune diabetes by race/ethnicity.
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