Functional polymorphism rs1024611 in the MCP1 gene is associated with the risk of varicose veins of lower extremities

Shadrina, Alexandra S.; Сметанина, М. А.; Sevost'ianova, Kseniya; Селиверстов, Е. И.; Ilyukhin, E. A.; Воронина, Е. Н.; Золотухин, И. А.; Филипенко, М. Л.

doi:10.1016/j.jvsv.2016.12.008

Cited by 10 publications

(8 citation statements)

References 28 publications

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“…However, none of these associations reached statistical significance after adjustment for multiple comparisons. For the polymorphic locus rs2010963 G > C in the VEGFA gene for the vascular endothelial growth factor, an association with a decreased risk of VVD was revealed, and its significance remained after applying the Bonferroni correction [18] . On the sample of ethnic Russians, we also revealed the association of functional SNP rs1024611 in the regulatory region of the MCP1 gene with the increased risk for primary VV development, which was prominent in C2-class patients, in patients younger than 30 years old at disease onset and in patients with negative anamnesis [19] .…”

Section: Genetic Association Studies On Varicose Vein Pathogenesis-an Overviewmentioning

confidence: 98%

The genetic constituent of varicose vein pathogenesis as a key for future treatment option development

Сметанина¹,

Шевела²,

Gavrilov³

et al. 2021

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This perspective focuses primarily on the fundamental part of phlebology, where most attention is paid to the genetic aspects of the pathogenesis of varicose vein disease and where the main breakthrough advances in this area of research are discussed. We propose a direction for further actions to replenish molecular genetic knowledge about the main drivers of pathological processes in varicose vein disease and to complete the creation of an entire picture of pathogenesis, which, in turn, may serve as a key for the development of treatment options in the future in order to translate research evidence into clinical practice.

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Section: Genetic Association Studies On Varicose Vein Pathogenesis-an Overviewmentioning

confidence: 98%

The genetic constituent of varicose vein pathogenesis as a key for future treatment option development

Сметанина¹,

Шевела²,

Gavrilov³

et al. 2021

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“…A previous report demonstrated that MCP-1 is associated with the risk of varicose veins in the lower extremities, and the abundance of MCP-1 protein suppresses the development of varicose veins in an animal model. 8) Our results indicate damage to the vessel walls of varicose veins because of hemodynamic causes, including venous hypertension, low shear stress, turbulent flow, stasis, and increase in inflammatory biomarker levels.…”

Section: Discussionmentioning

confidence: 62%

“…The involvement of MCP-1 in the development of primary varicose veins and inflammation could be implicated in the pathogenesis of CVI. 7,8) Interleukin-6 (IL-6) is secreted by T cells and macrophages to stimulate immune response to trauma or other tissue damage thus leading to inflammation.…”

Section: Introductionmentioning

confidence: 99%

Appropriate Surgical Treatment of Symptomatic Primary Varicose Veins Decreases Systemic Inflammatory Biomarkers

Arase

Sugasawa

Kawatani

et al. 2019

Annals of Vascular Diseases

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Objective: To evaluate the relationship between systemic inflammatory biomarkers and efficacy of surgical treatment of primary varicose veins of the lower extremities.Methods: Total 12 patients who underwent endovenous laser ablation or stripping of varicose veins and six healthy subjects were enrolled. Structural and molecular changes of varices were assessed by immunohistochemical staining with anti-monocyte chemotactic protein-1 (MCP-1). MCP-1 and interleukin-6 (IL-6) levels in systemic antecubital blood were measured before and at 12 weeks after treatment.Results: Immunohistochemical staining revealed prominent manifestation of MCP-1-positive endothelial cells in the walls of varices. Preoperative serum MCP-1 and IL-6 levels in the patients were significantly higher than those in the control (166±12 pg/mL vs 99±10 pg/mL, p=0.003; 5.1±0.95 pg/mL vs 0.0±0.0 pg/mL, p=0.001, respectively). The values were significantly correlated with the severity of chronic venous insufficiency (CVI). Postoperative serum MCP-1 level significantly decreased compared with the preoperative level (152±10 pg/mL vs 166±12 pg/mL, p=0.048). The values after endovenous laser ablation did not significantly decrease compared with those after stripping.Conclusion: Varicose veins with CVI increase inflammatory biomarker levels in the local tissue and systemic blood. Appropriate treatment of symptomatic varicose veins decreases inflammatory biomarker levels.

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“…Так, например, делеция ATTG в гене NFKB1 ассоциирована с низкой активностью его промотора, в результате которой меняется экспрессия продукта гена-мишени этого транскрипционного фактора -МСР-1 (белка хемо аттрактанта моноцитов 1), привлекающего моноциты к зоне воспаления [25,26]. Один из аллельных вариантов МСР-1 -rs1024611 G -повышает риск развития варикозной болезни [27].…”

Section: Review научный обзорunclassified

“…Среди прочих факторов, которые находятся под его контролем, -МСР-1. Напомним, что один из аллелей гена МСР-1 ассоциирован с развитием варикозной болезни нижних конечностей у этнических русских [27]. Этот хемокин, чья основная функция заключается в привлечении моноцитов к зоне повреждения и усилении пролиферации гладкомышечных клеток, повышении активности ММР-2, весьма вероятно, служит важным звеном механизма деградации компонентов венозной стенки и ее ремоделирования.…”

Section: потенциальные возможности фармакотерапииunclassified

Varicose veins: on the verge of discovering the cause?

et al. 2020

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Varicose veins of the lower limbs are one of the most common and wide-spread pathology all around the world. What triggers the specific changes in a vein wall still remains unclear as well as what happens in the layers of the vein wall after the disease starts. The aim of the article is to analyze published data and results of researches on epidemiology, genetics, cellular and molecular mechanisms underlying varicose veins pathogenesis. It is now commonly accepted that vein wall changes in patients with varicose veins result from vein-specific inflammation. This process includes leukocytes adhesion to venous endothelium with their subsequent migration into the vein wall and surrounding tissues. Activated leukocytes express a number of molecules that lead to vein wall remodeling and dilation. Comprehensive assessment of the epidemiological data on the prevalence of varicose veins and risk factors, of the findings from genetic studies, of data on molecular-cell interactions as well as results of various surgical interventions in patients with varicose veins, shows that remodeling is a reversible process that can be stopped and reversed by different stimuli including some chemical substances. For the first time in the literature, the authors assume that varicose veins can be successfully cured pharmacologically with no surgical interventions needed.

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Functional polymorphism rs1024611 in the MCP1 gene is associated with the risk of varicose veins of lower extremities

Cited by 10 publications

References 28 publications

The genetic constituent of varicose vein pathogenesis as a key for future treatment option development

The genetic constituent of varicose vein pathogenesis as a key for future treatment option development

Appropriate Surgical Treatment of Symptomatic Primary Varicose Veins Decreases Systemic Inflammatory Biomarkers

Varicose veins: on the verge of discovering the cause?

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