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The role of a nonsynonymous CD226 (DNAX‐accessory molecule‐1) variant (Gly 307Ser) in isolated Addison’s disease and autoimmune polyendocrinopathy type 2 pathogenesis
Author(s) -
Gan Earn H.,
Mitchell Anna L.,
MacArthur Katie,
Pearce Simon H. S.
Publication year - 2011
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2011.04030.x
Subject(s) - autoimmune disease , nonsynonymous substitution , immunology , autoimmunity , pathogenesis , allele , context (archaeology) , medicine , graves' disease , endocrinology , biology , disease , genetics , gene , genome , paleontology
Summary Context Genome‐wide association studies have discovered various susceptibility alleles that are shared among different autoimmune conditions, implicating several biochemical pathways in the pathogenesis of autoimmunity. A nonsynonymous polymorphism in exon 7 of the gene encoding the lymphocyte cell‐surface CD226 (DNAM1) receptor, Gly307Ser (rs763361), has recently been identified as conferring risk to many autoimmune disorders. We performed a case–control study to determine if the CD226 307Ser variant is also associated with autoimmune Addison’s disease (AAD). Patient and design We genotyped rs763361 in a UK cohort of 326 AAD subjects [183 with associated autoimmune conditions – autoimmune polyendocrinopathy syndrome type‐2 (APS2)] and 311 healthy controls, using a Taqman genotyping assay. Results The susceptibility ‘T’ allele at rs763361 was found in 50·5% of patients with AAD compared to 46·5% of controls ( P ‐value 0·16, OR 1·17; 95% CI 0·94–1·46). However, comparing the APS2 subgroup to healthy controls, the T allele was found in 53·8% vs 46·5% in controls (OR 1·34; CI 1·04–1·74, P ‐value 0·03). In contrast, the T allele frequency was 46·2% in isolated Addison’s disease ( P ‐value 0·94 vs healthy controls). Conclusion It seems likely that the 307Ser variant of the CD226 receptor is associated with APS2 because of its underlying association with type 1 diabetes and autoimmune thyroid disease. The strength of association in patients with isolated AAD appears to be weak or nonexistent compared to that in APS2.