HLA‐Associated Phenotypes in Youth with Autoimmune Diabetes. Issue 2 (23rd August 2012)

• Record Type: Journal Article
• Authors: Black, Mary Helen; Lawrence, Jean M; Pihoker, Catherine; Dolan, Lawrence M; Anderson, Andrea; Rodriguez, Beatriz; Marcovina, Santica M.; Mayer‐Davis, Elizabeth J; Imperatore, Giuseppina; Dabelea, Dana
• Is Part Of: Pediatric diabetes. Volume 14:Issue 2(2013)
• Page Start: 121
• Page End: 128
• Publication Date: 2012-08-23
• Subjects: Diabetes in children -- Periodicals; 616.462
• DOI: 10.1111/j.1399-5448.2012.00905.x
• Languages: English
• ISSNs: 1399-543X

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="pedi905-sec-0001" sec-type="section"> <title>Objectives</title> <p>To examine human leukocyte antigen <italic>HLA</italic> DRB1–DQB1 haplotypes within a multi‐ethnic cohort and assess their association with characteristics of diabetes onset.</p> </sec> <sec id="pedi905-sec-0002" sec-type="section"> <title>Methods</title> <p>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 <italic>HLA</italic> 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.</p> </sec> <sec id="pedi905-sec-0003" sec-type="section"> <title>Results</title> <p>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.</p> </sec> <sec id="pedi905-sec-0004" sec-type="section"> <title>Conclusions</title> <p>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.</p> </sec> </abstract>