CLINICAL, INSTRUMENTAL AND MOLECULAR-GENETIC CHARACTERISTICS OF PATIENTS WITH CHRONIC VENOUS INSUFFICIENCY OF THE LOWER EXTREMITIES AND THE ROLE OF THE MMP9 GLN279ARG POLYMORPHISM IN VENOUS WALL REMODELING

Abstract

Background. Chronic venous insufficiency (CVI) of the lower extremities is one of the most prevalent disorders of the human vascular system and a leading cause of disability among the working-age population. Matrix metalloproteinase 9 (MMP9) is a key effector of extracellular matrix degradation and venous wall remodeling, and the functional Gln279Arg (rs17576) polymorphism may modify individual susceptibility to the disease.Aim. To characterize the clinical, laboratory and ultrasonographic features of patients with CVI and to evaluate the association of the MMP9 Gln279Arg polymorphism with the risk of developing and progressing CVI 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) and 87 healthy controls of comparable age and sex. All participants underwent clinical examination, coagulation testing and duplex Doppler ultrasonography. The MMP9 Gln279Arg polymorphism was genotyped by polymerase chain reaction. Associations were assessed using the Pearson chi-square test and odds ratios (OR) with 95% confidence intervals (CI).Results. Telangiectasia (92%), limb oedema (87%), trophic skin lesions (77%) and varicose superficial veins (77%) dominated the clinical picture, while healed and active venous ulcers were present in 45% and 16% of patients, respectively. A tendency to hypercoagulation was observed, more pronounced in C5-C6 patients. Combined vertical and horizontal pathological refluxes were the leading ultrasonographic finding (38.7%). The unfavorable Arg allele (OR=1.3; 95% CI 0.82-1.95) and the Arg/Arg genotype (OR=1.3; 95% CI 0.59-3.08) were more frequent in patients; in the severe C5-C6 subgroup the Gln/Arg and Arg/Arg genotypes reached OR=1.2 and OR=1.4, respectively, whereas the Gln/Gln genotype showed a protective tendency (OR=0.7-0.8).Conclusion. The Gln279Arg polymorphism of the MMP9 gene contributes to venous wall remodeling and progressive valvular incompetence. The unfavorable Arg allele and Arg/Arg genotype are candidate predictors of CVI development and progression and may support a personalized, genetically informed preventive strategy.