Effects of Non-HLA Gene Polymorphisms on Development of Islet Autoimmunity and Type 1 Diabetes in a Population With High-Risk HLA-DR,DQ Genotypes

Andrea K. Steck*, Randall Wong, Brandie Wagner, Kelly Johnson, Edwin Liu, Jihane Romanos, Cisca Wijmenga, Jill M. Norris, George S. Eisenbarth, Marian J. Rewers

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

39 Citations (Scopus)

Abstract

We assessed the effects of non-HLA gene polymorphisms on the risk of islet autoimmunity (IA) and progression to type 1 diabetes in the Diabetes Autoimmunity Study in the Young. A total of 1,743 non-Hispanic, white children were included: 861 first-degree relatives and 882 general population children identified as having high-risk HLA-DR/DQ genotypes for type 1 diabetes. Of those, 109 developed IA and 61 progressed to diabetes. Study participants were genotyped for 20 non-HLA polymorphisms, previously confirmed as type 1 diabetes susceptibility loci. PTPN22 and UBASH3A predicted both IA and diabetes in regression models controlling for family history of type 1 diabetes and presence of HLA-DR3/4-DQB1*0302 genotype. In addition, PTPN2 predicted IA whereas INS predicted type 1 diabetes. The final multivariate regression models for both IA and type 1 diabetes included PTPN22, UBASH3A, and INS, in addition to family history of type 1 diabetes and HLA-DR3/4. In general population children, the most frequent combinations including these five significant predictors conferred hazard ratio of up to 13 for IA and >40 for type 1 diabetes. Non-HLA susceptibility alleles may help estimate risk for development of type 1 diabetes in the general population. These findings require replication in different populations. Diabetes 61:753-758, 2012

Original languageEnglish
Pages (from-to)753-758
Number of pages6
JournalDiabetes
Volume61
Issue number3
DOIs
Publication statusPublished - Mar-2012

Keywords

  • GENOME-WIDE ASSOCIATION
  • SUSCEPTIBILITY LOCI
  • MULTIPLEX FAMILIES
  • YOUNG DAISY
  • INSULIN
  • AUTOANTIBODIES
  • METAANALYSIS
  • PROGRESSION
  • CHILDREN
  • MELLITUS

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