Allelic variant in <i><scp>CTLA4</scp></i> is associated with thyroid failure and faster <i>β</i>‐cell exhaustion in latent autoimmune diabetes in adults <i>CTLA4</i>等位基因变异与成人迟发型自身免疫性糖尿病患者的甲状腺功能衰竭以及<i>β</i>‐细胞加速衰竭有关

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.