Abstract |
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.
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Authors | I L Ross, S Babu, T Armstrong, L Zhang, D Schatz, A Pugliese, G Eisenbarth, P Baker Ii |
Journal | Tissue antigens
(Tissue Antigens)
Vol. 84
Issue 4
Pg. 361-9
(Oct 2014)
ISSN: 1399-0039 [Electronic] England |
PMID | 25040682
(Publication Type: Comparative Study, Journal Article)
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Copyright | © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. |
Chemical References |
- Autoantibodies
- HLA-A*02:49 antigen
- HLA-A2 Antigen
- Steroid 21-Hydroxylase
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Topics |
- Addison Disease
(genetics, immunology)
- Adolescent
- Adult
- Autoantibodies
(immunology)
- Female
- HLA-A2 Antigen
(genetics, immunology)
- Humans
- Male
- Middle Aged
- Risk Factors
- South Africa
- Steroid 21-Hydroxylase
(immunology)
- United States
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