title: The role of a nonsynonymous CD226 (DNAX-accessory molecule-1) variant (Gly 307Ser) in isolated Addison's disease and autoimmune polyendocrinopathy type 2 pathogenesis.
abstract: BACKGROUND
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Human Genetics, Newcastle University, Newcastle upon Tyne, UK. Earn.gan@ncl.ac.uk
authors.forename: Earn H
authors.initials: EH
authors.lastname: Gan
authors.forename: Anna L
authors.initials: AL
authors.lastname: Mitchell
authors.forename: Katie
authors.initials: K
authors.lastname: Macarthur
authors.forename: Simon H S
authors.initials: SH
authors.lastname: Pearce
mesh_terms: D000224:Addison Disease / Q000235:genetics*; D000483:Alleles; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics*; D001327:Autoimmune Diseases / Q000235:genetics*; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020125:Mutation, Missense; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics*; D011110:Polymorphism, Genetic; D013959:Thyroid Diseases; D000098862:T Lineage-Specific Activation Antigen 1
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1