Diabetes, Metabolic Syndrome and Obesity (Sep 2022)
Association of CLTA-4 Gene Polymorphisms with Diabetes Mellitus: A Study Based on the Han Population of Northern China
Abstract
Dongyue Ren,1 Lin He,2 Xiaoling Pang1 1Department of Emergency, the Fourth Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China; 2Good Clinical Practice Institution, the Fourth Affiliated Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Xiaoling Pang, Department of Emergency, the Fourth Affiliated Hospital of China Medical University, No. 4 Chongshan East Road, Huanggu District, Shenyang, 110032, People’s Republic of China, Tel +86-18900913992, Email [email protected]: This study aimed to investigate the association of CLTA-4 gene polymorphism with Type 1 and 2 diabetes mellitus (DM) (T1DM and T2DM) in the Han population of northern China.Methods: A total of 234 Chinese Han DM patients and 187 non-diabetic subjects were included in the study. Two gene polymorphisms of the CLTA-4, including CTLA-4+49A/G (rs231775) and CTLA4-318C/T (rs5742909), were studied using polymerase chain reaction-restriction endonuclease fragment length polymorphism (PCR-RFLP) analysis. Chi-square analysis and Student’s t-test were performed to determine the distribution of the gene polymorphism and alleles at the locus of CTLA4-318C/T and CTLA4+49A/G among T1DM and T2DM patients with or without diabetic ketosis (DK), diabetic nephropathy (DN) or autoantibodies (Ab).Results: Our results indicated that the distribution frequencies of genotypes and alleles at the CTLA-4+49A/G and CTLA4-318C/T loci of T1DM patients were not significantly different from those of the controls. However, the distribution frequencies of genotypes and alleles at the CTLA-4+49A/G loci of T2DM patients were significantly different from the controls (P=0.024 for genotypes and P=0.004 for A and G alleles). Besides, the A and G alleles at the CTLA4-318C/T loci of T2DM DK+ patients showed significantly different distribution frequencies compared to those of the T2DM DK patients (P=0.001).Conclusion: Our data suggest that the gene polymorphisms of CTLA-4, including CTLA-4+49A/G and CTLA4-318C/T, are important predictors of DM. CTLA-4 may be a susceptibility gene for T2DM. Patients with T2DM carrying the T allele at the CTLA4-318 C/T locus are more predisposed to diabetic ketosis.Keywords: diabetes mellitus, gene polymorphism, CTLA-4, diabetic ketosis, diabetic nephropathy, autoantibodies