Allelic variant in CTLA4 is associated with thyroid failure and faster beta-cell exhaustion in latent autoimmune diabetes in adults

作者：Delitala Alessandro P^*; Fanciulli Giuseppe; Zoledziewska Magdalena; Pitzalis Maristella; Pusceddu Pierpaolo; Frongia Paola; Puddu Loreta; Errigo Alessandra; Maioli Margherita; Delitala Giuseppe; Pes Giovanni M

来源：Journal of Diabetes, 2015, 7(1): 68-73.

DOI：10.1111/1753-0407.12137

• cytotoxic T lymphocyte associated-4 (CTLA4)
• hypothyroidism
• latent autoimmune diabetes in adults
• beta-cell exhaustion

BackgroundThe 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).
MethodsThe 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 CTLA4G6230A variant was assessed in LADA, early and late-onset T1D patients as well as in the controls.
ResultsThe frequency of CTLA4G 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).
ConclusionsThe G6230ACTLA4 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.

• 出版日期2015-1