Abstract
Studies have demonstrated that polymorphic variants of arginase 1 gene (ARG1) are involved in human diseases, such as coronary heart disease, hypertension, and diabetes. Our study aimed to investigate the association between ARG1 rs2781666 single nucleotide polymorphism (SNP) and diabetic retinopathy (DR) in type 2 diabetes (T2DM) patients. Polymorphism was genotyped in 740 T2DM patients and 400 healthy individuals. A significant difference in the genotype distribution was observed between the patients and the controls. The T allele and TT genotype were associated with an increased risk of T2DM (OR 1.4, 95% CI 1.14–1.72, p = 0.001 and OR 2.16, 95% CI 1.23–3.80, p = 0.007, respectively). When the T2DM subjects were stratified into DR+ and DR− subgroups, the T allele and TT genotype frequencies were significantly higher in the DR+ group compared to the DR− group, demonstrating OR 1.68 (1.33–2.12), p < 0.0001 and OR 2.39 (1.36–4.18), p = 0.002, respectively. Logistic regression analysis was applied to determine the interaction between the ARG1 genotypes and other risk factors. Only ARG1 rs2781666 SNP was a significant risk predictor of DR (p = 0.003). In conclusion, this is the first report discussing the effect of ARG1 polymorphism on the microvascular complications that are associated with diabetes. Our findings demonstrate that ARG1 rs2781666 SNP is significantly associated with an increased susceptibility to DR in T2DM patients.
Highlights
Type 2 diabetes mellitus (T2DM) is a chronic, heterogeneous disorder of the glucose metabolism that affects over 450 million people around the world [1]
The genotype of the rs2781666 single nucleotide polymorphism (SNP) in the arginase1 gene was analyzed in 740 T2DM patients and 400 healthy individuals, with a genotyping success rate 100%
All of the results were compared between this subgroup (DR+) and the 477 T2DM patients who did not present with retinopathy (DR−)
Summary
Type 2 diabetes mellitus (T2DM) is a chronic, heterogeneous disorder of the glucose metabolism that affects over 450 million people around the world [1] Diabetic microvascular complications, such as diabetic nephropathy, retinopathy, and neuropathy, are an important cause of morbidity and mortality in T2DM patients [2]. An important enzyme in the urea cycle, utilizes L-arginine as a substrate to produce urea and ornithine It is expressed in several cell types, including endothelial cells, macrophages, and vascular smooth muscle cells [4]. Uncoupled NOS produces superoxide instead of nitric oxide (NO), which causes the production of the proinflammatory oxidant peroxynitrite This may lead to vascular dysfunction in a range of diseases, including diabetes [5,6]. Studies in animal models have reported that of diabetes increases in the levels of arginase contribute to endothelial cell dysfunction [7,8,9]
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