The effect of the A82G mutation in the MMP-12 gene and C634G mutation in the VEGF-A gene on the course of lower limb varicose veins and the risk of disease recurrence

Abstract

Aim: creation of a method for predicting the development of varicose veins of the lower extremities and its recurrence.Object and methods. 2 independent studies of patients with C2-C6 varicose veins of the lower extremities (CEAP-classifier) were conducted. In the first, with ultrasound diagnosis of the main veins of the lower extremities and genomic analysis of blood samples, 75 participants (men 20, women 55), mean age 43.7 ± 5.9 years. All patients were randomized into two groups: group I (n = 17) – with recurrent varicose veins; Group II (n = 58) – applied with varicose veins for the first time. The 2nd study involved 44 (men 10, women 34), mean age 55.5 ± 2.7 years. Similarly, patients were divided into groups – I (5) and II (39 people). All patients of the first stage of the study underwent real-time PCR with allele-specific primers to determine the A82G mutation in the MMP-12 gene (matrix metalloproteinase-12) and the second stage C634G in the VEGF-A gene (endothelial fibroblast growth factor – A).Results of the study. In patients of both groups I and II, having the MMP-12 gene in the heterozygous variant, dilatation of the tibial and popliteal veins was present (6.4 ± 0.3 mm and 10.7 ± 0.24 mm, respectively) with the presence reflux and slowing down the evacuation of blood from the deep venous system. In patients of group I, the MMP-12 gene was found in 80 % of cases, as A/A (homozygous) and A/G (heterozygous variation), while in group II only in 33.3 % of cases. Pearson's goodness-of-fit criterion χ2 = 10.4 (the critical value of the criterion is 6.63), p < 0.01. The frequency of recurrence of varicose veins and mutation of the MMP-12 gene according to the Spearman test was 1.0 with the number of degrees of freedom 23, p < 0.05. In the 2nd study, a correlation was found between groups I and II of patients with the C/C genotype (Pearson's coefficient χ2 = 0.79, p < 0.11) and a correlation in the duration of the disease between groups of patients with the C/C genotype (homozygous variation) and C /G (heterozygous variation) – Pearson correlation coefficient χ2 = 0.92 (p < 0.01).Conclusion. The revealed relationship between the MMP-12 gene polymorphism and the frequency of varicose vein recurrence is a predictor of the development of structural changes in the vein wall, and a mutation in the VEGF-A gene occurs with a long history of the disease.

Keywords

• varicose veins of the lower extremities
• recurrence of varicose veins
• gene mutation
• vegf-a
• mmp-12