THE VEGFA G634C (RS2010963) POLYMORPHISM AND IMPAIRED ANGIOGENESIS IN THE PATHOGENESIS OF DIABETIC FOOT SYNDROME IN PATIENTS WITH TYPE 2 DIABETES MELLITUS
DOI:
https://doi.org/10.17605/Keywords:
VEGFA; rs2010963; G634C polymorphism; angiogenesis; diabetic foot syndrome; type 2 diabetes mellitus; single-nucleotide polymorphism.Abstract
Background. Vascular endothelial growth factor A (VEGFA) is the principal regulator of angiogenesis, a process that is critically impaired in the diabetic foot syndrome (DFS). The functional G634C (rs2010963) polymorphism in the VEGFA gene modulates circulating VEGF levels, but its contribution to DFS susceptibility and to the distinct clinical forms of the disease has not been characterized in Central Asian patients.
Aim. To determine the distribution of the VEGFA G634C polymorphism in patients with DFS and controls, and to assess its association with DFS and with the neuropathic and neuroischemic forms of the disease.
Materials and methods. The G634C polymorphism was genotyped by polymerase chain reaction in 96 patients with type 2 diabetes and DFS (35 neuropathic, 61 neuroischemic) and in 83 control subjects without diabetes. Allele and genotype frequencies were compared using the χ² test and the odds ratio (OR) with 95 % confidence intervals (CI); conformity to Hardy–Weinberg equilibrium was verified.
Results. Genotype distributions conformed to Hardy–Weinberg equilibrium in both groups. The minor C allele was more frequent in DFS patients than in controls (24.5 % vs 10.8 %; OR = 2.7, 95 % CI 1.5–4.74). The heterozygous G/C genotype (32.3 % vs 16.9 %; OR = 2.4, 95 % CI 1.16–4.76) and the homozygous C/C genotype (8.3 % vs 2.4 %; OR = 3.7, 95 % CI 0.83–16.25) were associated with increased DFS risk, whereas the G allele and G/G genotype were protective. The risk markers were expressed in both clinical forms, and the heterozygous G/C genotype was somewhat more frequent in the neuroischemic form, in which it accompanied a marked reduction of tissue oxygenation.
Conclusion. The C allele and the C-bearing genotypes of the VEGFA G634C polymorphism are associated with susceptibility to DFS in patients with type 2 diabetes, supporting a role for genetically determined impairment of angiogenesis in the pathogenesis of the syndrome.
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