Multiple Loci in the HLA Complex Are Associated with Addison's Disease

作者：Skinningsrud Beate^*; Lie Benedicte A; Lavant Ewa; Carlson Joyce A; Erlich Henry; Akselsen Hanne E; Gervin Kristina; Wolff Anette B; Erichsen Martina M; Lovas Kristian; Husebye Eystein S; Undlien Dag E

来源：Journal of Clinical Endocrinology & Metabolism, 2011, 96(10): E1703-E1708.

DOI：10.1210/jc.2011-0645

Context: 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.
Objective: 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.
Design: HLA-A, -B, -DRB1, and -DQB1 and a microsatellite in MICA were genotyped in 414 AAD patients and 684 controls of Norwegian origin.
Results: 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 x 10(-20)]. After conditioning on DRB1, association with AAD was still present for HLA-B and MICA, suggesting the presence of additional risk factors.
Conclusions: The major histocompatibility complex harbors multiple risk loci for AAD, in which DRB1 appears to represent the main risk factor. (J Clin Endocrinol Metab 96: E1703-E1708, 2011)

• 出版日期2011-10
• 单位河北医科大学