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Latent autoimmune diabetes in adults (LADA) is identified by the presence of GAD65 autoantibodies in diabetic patients who do not require insulin treatment for at least six months after the diagnosis. Previous studies have shown that the risk for LADA, similarly to type 1 diabetes mellitus (T1DM), is increased in subjects carrying the HLA-DRB1*03-DQA1*0501-DQB1*0201 and/or HLA-DRB1*04-DQA1*0301-DQB1*0302 haplotypes. In the present study, we investigated the association between LADA and the CTLA-4 A/G polymorphism, another gene polymorphism associated with T1DM and other autoimmune diseases. The heterozygous A/G genotype was significantly more frequent among 80 LADA (69%) than among 85 healthy subjects of similar age and geographical provenience (47%) (OR = 2.47, corrected P= 0.023). Conversely, the homozygous A/A genotype was significantly less frequent in LADA subjects than in healthy controls (26% vs. 47%, OR = 0.4, corrected P= 0.028). The results of our study show that LADA is positively associated with the CTLA-4 A/G genotype, similarly to T1DM, thus providing further supporting evidence of the autoimmune origin of this form of diabetes mellitus of the adult.

Slowly progressive insulin-dependent diabetes mellitus (IDDM), like classical IDDM, is also associated with genetic markers. HLA-DR3 but not DR4 is associated with latent autoimmune diabetes in adults (LADA). In GAD65 antibody-positive Finnish LADA patients, DQB1*0302 is positively associated with the disease. Alleles of the MHC class I chain-related A (MICA) gene located centromeric to the HLA-B gene is associated with LADA. Allele 5.1 of MICA was associated with both LADA and adult-onset Italian IDDM patients when compared to controls. This finding was also observed in Indian and Latvian patients with LADA. These findings suggest that certain genetic markers distinguish LADA better.