Low level of plasma VEGF-A and C allele of -2578*C/A polymorphism in the VEGF-A gene are risk factors of diabetic foot ulcer in Javanese ethnic

Abstract

Diabetes mellitus (DM) is caused by abnormal insulin secretion, impaired insulin action, or both. Approximately 12-25% of type 2 diabetes mellitus (T2DM) patients will develop diabetic foot ulcers (DFU). Vascular endothelial growth factor (VEGF) is a group of platelet-derived growth factors (PDGF) which have a potential role in angiogenesis. Low levels of VEGF-A can cause insufficient angiogenesis leading to wound healing inhibition. The 2578*C/A polymorphism of VEGF-A gene has been reported as a candidate marker for the DFU development. However, the variant role in the development of DFU in Javanese ethnic needs to be clarified. This study was conducted to compare VEGF-A levels and the -2578*C/A polymorphism of the VEGF gene among diabetic patients with and without DFU in Javanese ethnic. In this case-control study, the T2DM individuals with DFU as case group (n=19) and without DFU as control group (n=41) were recruited. The VEGF-A levelswere determined by ELISA. The ARMS-PCR technique was applied to investigate the presence of -2578*C/A polymorphism of the VEGF gene. Data were analyzed with independent t, Mann-Whitney, Chi-square, and Kruskal-Wallis tests with significance level of p<0.05. The median of plasma VEGF-A level was significantly different between case and control groups (p=0.001). The genotype frequency of -2578*C/A polymorphism of VEGF gene was no difference between case and control groups. However, individuals with C allele have a higher risk factor to develop DFU than A allele (CC+CA vs AA;p=0.042; OR=2.5). The plasma VEGF-A levels were lower in T2DM subjects with DFU than those without DFU. In conclusion,individuals with C allele of -2578*C/A polymorphism of VEGF gene are more susceptible to have DFU than individuals with A allele in Javanese ethnic with T2DM.