cytotoxic t lymphocyte antigen-4 gene variants in type 2 diabetic patients with or without neuropathy

many studies have shown that cytotoxic t lymphocyte antigen-4 (ctla-4) gene variants are associated with several autoimmune diseases particularly type 1 diabetes. due to the lack of consistent data for this association with type 2 diabetes (t2d), this study explored the possible influence of ctla-4 gene polymorphisms at -1722 (t/c), -318 (c/t), and +49 (g/a) positions for susceptibility to t2d in relation with neuropathy. one hundred and eleven unrelated patients with t2d [49 patients with diabetic peripheral neuropathy (dpn) and 62 patients without pdn] and 100 healthy ethnic- and gender-matched controls were included in this study. the dimorphisms at -1722 (c/t), -318 (c/t) and +49 (a/g) for ctla-4 gene were determined using arms-pcr. the ctla-4 (+49 g/g) and (+49 a/a) genotypes were found to be positively and negatively associated with t2d, respectively ( p =0.03). the -318 c/t and t/t genotypes were more frequent in patients than controls and -318 c/c genotype was shown to be protective for t2d ( p =0.003). act and gtt haplotypes were less and more frequent in controls and patients, respectively ( p =3.86×10 -7 and p =2.29×10 -5 ). genotypes distribution among t2d patients with and without dpn compared to healthy controls showed significantly lower frequencies for -318 c/c and +49 a/a genotypes and significantly higher frequencies for -318 c/t and t/t genotypes as well. our findings indicate that ctla-4 (+49 a/g) and (-318 c/t) genotypes could be considered as genetic risk factors associated with susceptibility or protection for t2d.