title: Allelic variant in CTLA4 is associated with thyroid failure   and faster β-cell exhaustion in latent autoimmune   diabetes in adults.
abstract: BACKGROUND
  The aim of the study was to investigate the role of the cytotoxic T-lymphocyte-associated protein 4 (CTLA4) G6230A variant on the susceptibility of latent autoimmune diabetes in adults (LADA) as a whole and in the subset of patients who share autoimmune thyroid disease (AITD).
  
  
  METHODS
  The study included 202 LADA, 1373 patients with early onset type 1 diabetes (T1D), 130 patients with late-onset T1D, 188 patients with non-autoimmune diabetes and 1904 healthy controls. Thyrotropin (thyrotropin-stimulating hormone; TSH) and antibodies against thyroid peroxidase were analyzed in all patients. The CTLA4 G6230A variant was assessed in LADA, early and late-onset T1D patients as well as in the controls.
  
  
  RESULTS
  The frequency of CTLA4 G alleles and genotypes in LADA patients did not differ significantly from that in the other groups, regardless of its association with AITD. We found an increased frequency of G allele-containing genotypes within LADA patients who had higher TSH compared with those with normal TSH (P = 0.002). Moreover, LADA patients carrying G allele-containing genotypes were more likely to require insulin therapy within 4 years of diagnosis (P = 0.002).
  
  
  CONCLUSIONS
  The G6230A CTLA4 variant does not confer susceptibility to LADA in Sardinian patients even when associated with AITD. However, it helps identify a particular subset of LADA patients with more clinically severe disease, both for thyroid dysfunction and diabetes.
authors.forename: Alessandro P
authors.initials: AP
authors.lastname: Delitala
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Fanciulli
authors.forename: Magdalena
authors.initials: M
authors.lastname: Zoledziewska
authors.forename: Maristella
authors.initials: M
authors.lastname: Pitzalis
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Pusceddu
authors.forename: Paola
authors.initials: P
authors.lastname: Frongia
authors.forename: Loreta
authors.initials: L
authors.lastname: Puddu
authors.forename: Alessandra
authors.initials: A
authors.lastname: Errigo
authors.forename: Margherita
authors.initials: M
authors.lastname: Maioli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Delitala
authors.forename: Giovanni M
authors.initials: GM
authors.lastname: Pes
mesh_terms: D000328:Adult; D000368:Aged; D060908:CTLA-4 Antigen / Q000235:genetics*; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D011446:Prospective Studies; D013959:Thyroid Diseases / Q000209:etiology* / Q000473:pathology
chemical_list: D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human