Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 15 3 2016 06 26 220 228 EN Javad Kiani Division of Endocrinology, Department of Internal Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran Saedeh Khadempar Department of Biology, Sanandaj Branch, Islamic Azad University, Kurdistan, Iran Mehrdad Hajilooi Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran Hamzeh Rezaei Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran Fatemeh Keshavarzi Department of Biology, Sanandaj Branch, Islamic Azad University, Kurdistan, Iran Ghasem Solgi Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran AND Molecular Immunology Research Group, Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran 2015 11 04 2016 02 14 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. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/653 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/653/637