THE C936T POLYMORPHISM OF THE VEGFA GENE AS A GENETIC PREDICTOR OF THE DEVELOPMENT AND PROGRESSION OF CHRONIC VENOUS INSUFFICIENCY OF THE LOWER EXTREMITIES
DOI:
https://doi.org/10.17605/Keywords:
Chronic venous insufficiency; VEGFA; C936T; rs3025039; vascular endothelial growth factor; endothelial dysfunction; genetic predictor; CEAP.Abstract
Background. Vascular endothelial growth factor A (VEGFA) is a key regulator of angiogenesis and of the integrity and tone of the venous wall. The functional C936T (rs3025039) polymorphism, located in the 3' untranslated region of the gene, may modify susceptibility to chronic venous insufficiency (CVI), but data in different populations remain inconsistent.
Aim. To evaluate the contribution of the VEGFA C936T polymorphism to the risk of developing and progressing CVI of the lower extremities in an ethnically defined cohort from the Fergana Valley of Uzbekistan.
Materials and methods. A case-control study included 98 patients with CVI (CEAP classes C3-C6; 45 with C3-C4 and 53 with C5-C6) and 87 healthy controls of comparable age and sex. The C936T polymorphism was genotyped by polymerase chain reaction. Allele and genotype frequencies were compared using the Pearson chi-square test, and the strength of association was expressed as the odds ratio (OR) with a 95% confidence interval (CI).
Results. The unfavorable T allele was significantly more frequent in patients than in controls (22.4% vs 13.2%; OR=1.9; 95% CI 1.1-3.28; p=0.025), while the C/C genotype showed a protective effect (62.3% vs 77.0%; OR=0.5; 95% CI 0.26-0.93; p=0.05). The heterozygous C/T genotype (OR=1.8; 95% CI 0.92-3.58) and the homozygous T/T genotype (OR=2.2; 95% CI 0.56-8.36) were more frequent in patients. The association was strongest in the C3-C4 subgroup, in which the T allele reached OR=2.3 (95% CI 1.19-4.26; p=0.025) and the C/C genotype was protective (OR=0.4; 95% CI 0.19-0.88; p=0.025).
Conclusion. The C936T polymorphism of the VEGFA gene is a genetic predictor of CVI: the T allele and the C/T and T/T genotypes are associated with increased risk through promotion of endothelial dysfunction, whereas the C/C genotype is protective. Genotyping of this variant may support early, genetically informed prediction and prevention of CVI.
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