HLA-associated phenotypes in youth with autoimmune diabetes

Pediatr Diabetes. 2013 Mar;14(2):121-8. doi: 10.1111/j.1399-5448.2012.00905.x. Epub 2012 Aug 23.

Abstract

Objectives: To examine human leukocyte antigen HLA DRB1-DQB1 haplotypes within a multi-ethnic cohort and assess their association with characteristics of diabetes onset.

Methods: The sample included 1662 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 (FCP) 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.

Results: 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 FCP 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.

Conclusions: The distribution of DRB1-DQB1 haplotypes and their association with onset-related characteristics of autoimmune diabetes varies across major racial/ethnic groups in the USA. This may contribute to variation in clinical presentation of autoimmune diabetes by race/ethnicity.

Publication types

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

MeSH terms

  • Adolescent
  • African Continental Ancestry Group / genetics
  • C-Peptide / blood
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / genetics*
  • European Continental Ancestry Group / genetics
  • Female
  • Genetic Predisposition to Disease
  • HLA Antigens / genetics*
  • HLA-DQ beta-Chains / genetics*
  • HLA-DRB1 Chains / genetics*
  • Haplotypes*
  • Hispanic Americans / genetics
  • Humans
  • Male
  • Phenotype
  • Young Adult

Substances

  • C-Peptide
  • HLA Antigens
  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen
  • HLA-DRB1 Chains

Grant support