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Beate Skinningsrud, Benedicte A. Lie, Ewa Lavant, Joyce A. Carlson, Henry Erlich, Hanne E. Akselsen, Kristina Gervin, Anette B. Wolff, Martina M. Erichsen, Kristian Løvås, Eystein S. Husebye, Dag E. Undlien, Multiple Loci in the HLA Complex Are Associated with Addison's Disease, The Journal of Clinical Endocrinology & Metabolism, Volume 96, Issue 10, 1 October 2011, Pages E1703–E1708, https://doi.org/10.1210/jc.2011-0645
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Abstract
A strong association between autoimmune Addison's disease (AAD) and major histocompatibility complex class II-encoded HLA-DRB1-DQA1-DQB1 haplotypes is well known. Recent evidence from other autoimmune diseases has suggested that class I-encoded HLA-A and HLA-B gene variants confer HLA-DRB1-DQA1-DQB1-independent effects on disease.
We aimed to explore AAD predisposing effects of HLA-A and -B and further investigate the role of MICA and HLA-DRB1-DQA1-DQB1 in a much larger material than has previously been studied.
HLA-A, -B, -DRB1, and -DQB1 and a microsatellite in MICA were genotyped in 414 AAD patients and 684 controls of Norwegian origin.
The strongest association was observed for the DRB1 locus, in which the DRB1*03:01 and DRB1*04:04 conferred increased risk of AAD, particularly in a heterozygous combination [odds ratio 22.13; 95% confidence interval (11.39–43.98); P = 6 × 10−20]. After conditioning on DRB1, association with AAD was still present for HLA-B and MICA, suggesting the presence of additional risk factors.
The major histocompatibility complex harbors multiple risk loci for AAD, in which DRB1 appears to represent the main risk factor.