Abstract
Diabetic vascular complications are one of the main causes of death and disability. Previous studies have reported that genetic variation is associated with diabetic vascular complications. In this study, we aimed to investigate the association between GRB10 polymorphisms and susceptibility to type 2 diabetes mellitus (T2DM) vascular complications. Eight single nucleotide polymorphisms (SNPs) in the GRB10 gene were genotyped by MassARRAY system and 934 patients with type 2 diabetes mellitus (T2DM) were included for investigation. We found that GRB10 rs1800504 CC+CT genotypes were significantly associated with increased risk of coronary heart disease (CHD) compared with TT genotype (OR = 2.24; 95%CI: 1.36–3.70, p = 0.002). Consistently, levels of cholesterol (CHOL) (CC+CT vs. TT, 4.44 ± 1.25 vs. 4.10 ± 1.00 mmol/L; p = 0.009) and low density lipoprotein cholesterin (LDL-CH) (CC+CT vs. TT, 2.81 ± 1.07 vs. 2.53 ± 0.82 mmol/L; p = 0.01) in T2DM patients with TT genotype were significant lower than those of CC+CT genotypes. We further validated in MIHA cell that the total cholesterol (TC) level in GRB10-Mut was significantly reduced compared with GRB10-WT; p = 0.0005. Likewise, the reversed palmitic acid (PA) induced lipid droplet formation in GRB10-Mut was more effective than in GRB10-WT. These results suggest that rs1800504 of GRB10 variant may be associated with the blood lipids and then may also related to the risk of CHD in patients with T2DM.
Highlights
Diabetes is a metabolic disease that is characterized by hyperglycemia
We studied the influence of Growth factor receptor-binding protein 10 (GRB10) gene polymorphism on cardiovascular complications in patients with type 2 diabetes mellitus (T2DM)
After adding palmitic acid (PA) (100 μM) to MIHA cells transfected with GRB10WT, GRB10-Mut, and the empty vector, we found that the overexpression of GRB10 reversed the formation of lipid droplets induced by PA, and we discovered that the inhibitory effect of the GRB10-Mut vector had the most significant effect (Figure 3F)
Summary
Diabetes is a metabolic disease that is characterized by hyperglycemia. This disease is caused by abnormal glucose, lipid, and protein metabolism. This leads to impaired insulin secretion, insulin resistance, or both. T2DM is caused by ineffective use of insulin by the body. T2DM patients are characterized by high blood sugar, relative lack of insulin, insulin resistance and so on [1]. Statistical evidence shows that T2DM accounts for more than 95% of all diabetic cases in the Chinese population [2]. T2DM is becoming an increasingly serious problem for global health.
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