title: A cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphism is associated with autoimmune Addison's disease in English patients.
abstract: OBJECTIVE
  Recent studies have demonstrated an association between a microsatellite polymorphism of the CTLA-4 gene, specifically a 106 base pair allele, and both Graves' disease and autoimmune hypothyroidism. The aim of the present study was to determine whether the same polymorphism of the CTLA-4 gene was associated with autoimmune Addison's disease.
  
  
  METHODS
  We analysed a microsatellite polymorphism (variant lengths of a dinucleotide (AT)n repeat) within exon 3 of the CTLA-4 gene in the following groups: 21 English patients with non-associated Addison's disease, 18 with autoimmune polyglandular syndrome type 2 (APS2) and 173 healthy control subjects; 26 Norwegian patients with non-associated Addison's disease, 9 with autoimmune polyglandular syndrome type 1 (APS1), 17 with APS2 and 100 controls; 3 Finnish patients with non-associated Addison's disease, 5 with APS2 and 71 controls; 10 Estonian patients with non-associated Addison's disease, 2 with APS2 and 45 controls.
  
  
  METHODS
  The CTLA-4 microsatellite gene polymorphisms were determined by polymerase chain reaction amplification of genomic DNA and resolution of the products on sequencing gels.
  
  
  RESULTS
  The frequency of the 106 base pair allele was significantly increased in the groups of English patients with either non-associated Addison's disease or APS2 (P = 0.02 and 0.04, respectively), when compared to healthy controls with no clinical evidence or family history of either Addison's disease or any other autoimmune disorder. For Norwegian patients with either non-associated Addison's disease, APS1 or APS2, there was no association (P = 0.69, 0.62 and 0.97, respectively). This was also the case for Finnish patients with either non-associated Addison's disease or APS2 (P = 0.23 and 0.28, respectively) and for Estonian patients with either non-associated Addison's disease or APS2 (P = 0.34 and 0.29, respectively).
  
  
  CONCLUSIONS
  These results indicate that differences exist in the frequency of the 106 base pair allele in different population groups and in only the English population was the 106 base pair allele associated with Addison's disease.
authors: Section of Medicine, Northern General Hospital, University of Sheffield, UK. e.h.kemp@sheffield.ac.uk
authors: E H
authors: EH
authors: Kemp
authors: R A
authors: RA
authors: Ajjan
authors: E S
authors: ES
authors: Husebye
authors: P
authors: P
authors: Peterson
authors: R
authors: R
authors: Uibo
authors: H
authors: H
authors: Imrie
authors: S H
authors: SH
authors: Pearce
authors: P F
authors: PF
authors: Watson
authors: A P
authors: AP
authors: Weetman
mesh_terms: D000069594:Abatacept; D000224:Addison Disease / Q000208:ethnology / Q000235:genetics*; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D001327:Autoimmune Diseases / Q000208:ethnology / Q000235:genetics*; D060908:CTLA-4 Antigen; D016009:Chi-Square Distribution; D004739:England; D004957:Estonia; D005387:Finland; D020022:Genetic Predisposition to Disease; D006801:Humans; D018796:Immunoconjugates; D018895:Microsatellite Repeats / Q000235:genetics*; D009664:Norway; D011110:Polymorphism, Genetic
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D000069594:Abatacept