title: Cytotoxic T Lymphocyte Antigen-4 Gene Variants in Type 2 Diabetic Patients with or without Neuropathy.
abstract: 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.
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
authors.forename: Javad
authors.initials: J
authors.lastname: Kiani
authors.affiliation: Department of Biology, Sanandaj Branch, Islamic Azad University, Kurdistan, Iran.
authors.forename: Saedeh
authors.initials: S
authors.lastname: Khadempar
authors.affiliation: Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Hajilooi
authors.affiliation: Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
authors.forename: Hamzeh
authors.initials: H
authors.lastname: Rezaei
authors.affiliation: Department of Biology, Sanandaj Branch, Islamic Azad University, Kurdistan, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Keshavarzi
authors.affiliation: 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.
authors.forename: Ghasem
authors.initials: G
authors.lastname: Solgi
mesh_terms: D000328:Adult; D060908:CTLA-4 Antigen / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000276:immunology; D003929:Diabetic Neuropathies / Q000235:genetics* / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human
keywords: CTLA-4 antigen; Diabetes mellitus Type 2; Genes