HLA similarities indicate shared genetic risk in 21-hydroxylase autoantibody positive South African and United States Addison's disease

I. L. Ross, S. Babu, T. Armstrong, L. Zhang, D. Schatz, A. Pugliese, G. Eisenbarth, P. Baker

Research output: Contribution to journalArticle

4 Scopus citations


Genetic similarities between patients from the United States and South African (SA) Addison's Disease (AD) strengthen evidence for genetic association. SA-AD (n=73), SA healthy controls (N=78), and US-AD patients (N=83) were genotyped for DQA1, DQB1, DRB1, and HLA-B alleles. Serum was tested for the quantity of 21OH-AA and IFNα-AA at the Barbara Davis Center. Although not as profound as in US-AD, in SA-AD 21OH-AA+subjects the predominantly associated risk haplotypes were DRB1*0301-DQB1*0201 (DR3), DRB1*04xx-DQB1*0302 (DR4), and the combined DR3/4 genotype. DQB1*0302 associated DRB1*04xx haplotypes conferred higher risk than those DRB1*04xx haplotypes associated with other DQB1 alleles. We found negative association in 21OH-AA+SA-AD for DQA1*0201-DQB1*0202 and DQA1*0101-DQB1*0501 vs SA controls, and positive association for DQA1*0401-DQB1*0402 vs US-AD. Apart from the class II DR3 haplotype, HLA-B8 did not have an independent effect; however together DR3 and HLA-B8 conferred the highest risk vs 21OH-AA negative SA-AD and SA-controls. HLA-B7 (often with DR4) conferred novel risk in 21OH-AA+SA-AD vs controls. This study represents the first comparison between South African and United States AD populations utilizing genotyping and serology performed at the same center. SA-AD and US-AD 21OH-AA+patients share common HLA risk haplotypes including DR4 (with HLA-B7) and DR3 (with HLA-B8), strengthening previously described HLA associations and implicating similar genetic etiology.

Original languageEnglish (US)
Pages (from-to)361-369
Number of pages9
JournalTissue Antigens
Issue number4
StatePublished - Oct 1 2014



  • Addison's disease
  • Autoantibody serology
  • Autoimmune polyendocrine syndrome type 2
  • Human leukocyte antigen genetics

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Genetics

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