The CTLA4 protein is a member of the co-stimulatory family. It has homology to CD28 and binds the B7 family of ligands.
Because of its inhibitory effect on T-cell responses, polymorphisms in the CTLA4 gene have been strongly associated with insulin-dependent diabetes mellitus, Graves disease, Hashimoto thyroiditis, celiac disease, systemic lupus erythematosus, thyroid-associated orbitopathy, and other autoimmune diseases.
Alfadhli and Nizam (2013) cloned and sequenced the CTLA4 gene from 66 Kuwaiti patients with various autoimmune disorders (SLE, Rheumatoid Arthritis, and Hashimoto’s Thyroiditis), and compared the spliced variants in this gene in these patients from that in 22 healthy controls. Six variants were detected in this population; mCTLA4-672, sCTLA4-562, L-CTLA4-277, ssCTLA4-214, N-CTLA4-292, and K-CTLA4-142bp. The latter two variants were novel variants in this gene. Patients with SLE and Rheumatoid Arthritis showed a reduced frequency of the mCTLA4-672 and sCTLA4-562 variants, while N-CTLA4-292 was found to be reduced in all patients. Alfadhli and Nizam (2013) concluded that the expression pattern of the CTLA4 gene could also be playing a role in autoimmunity.
Zalloua et al. (2004) evaluated the role of the A49G polymorphism in exon 1 of the CTLA4 gene as a risk factor for type 1 diabetes in the Lebanese population. The CTLA4 G allele was found to be more frequently present in patients with type 1 diabetes (32%) than in control individuals (24%). The GG genotype was also significantly higher among patients (13%) than in controls (4%). Furthermore, in HLA-DQB1*0201-positive patients with type 1 diabetes, the GG and AA genotypes were higher and lower, respectively, than those found in control individuals.