Skinningsrud B, Husebye ES, Pearce SH, McDonald DO, Brandal K, Bøe Wolff A, Løvås K, Egeland T, Undlien DE
Polymorphisms in CLEC16A and CIITA at 16p13 are associated with primary adrenal insufficiency. [JOURNAL ARTICLE]
J Clin Endocrinol Metab 2008 Jul 1.
Context/objectives: It is known that different autoimmune diseases often share the same susceptibility genes. In this study we aimed to investigate if loci found associated with common autoimmune diseases in recent genome wide association studies, also could be susceptibility loci for autoimmune Addison's disease (primary adrenal insufficiency). Design/patients: A total of 139 tagging SNPs in eleven candidate genes (IL2, IL21, IL2RA, CLEC2D, CD69, ERBB3, PTPN11, SH2B3, CLEC16A, CIITA and PTPN2) were genotyped in a case/control study design consisting of Norwegian Addison's disease patients (n = 332) and Norwegian healthy control individuals (n = 1029). Five SNPs were subsequently selected for analysis in a United Kingdom sample set consisting of Addison's disease patients (n =210) and controls (n = 191).
Results: Polymorphisms in CLEC16A and CIITA remained significantly associated with Addison's disease in the Norwegian sample set at the 0.05 level, even after correction for multiple testing. CLEC16A and CIITA are both located at 16p13, but linkage disequilibrium patterns and logistic regression analyses suggest that SNPs in these two genes are independently associated with Addison's disease. We were not able to confirm these associations in the UK material, however, this may well be due to limited sample size and lack of statistical power.
Conclusion: Two alleles at 16p13 are independently associated with risk of Addison's disease in the Norwegian population, suggesting this chromosomal region to harbour common autoimmunity gene(s), CLEC16A and CIITA being possible independent candidates.
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