Varicose veins disease is widespread and affects all segments of population. Researchers are actively looking for molecular genetic mechanisms of this disease. Nevertheless, pathogenesis is still not completely clear. The authors describe the most interesting researches devoted to genetics and molecular technologies related to varicose veins over the past 5 years. Of course, this review does not clearly define pathogenesis of disease. In addition to collection of material and databases, many authors analyze the issue of regulation of gene expression. PIEZO1 gene is one of the perspective ones. Its rare variant (PTV) correlated with necessary surgical treatment of varicose veins. Many authors have been recently interested in regulatory RNAs. Their role is obvious in pathogenesis of varicose veins and complications. The most interesting ones are miR-202, miR-1202 and miR-661. Homeostasis of organism and its regulation are also important. Evidence of relationship between changes of certain microelements with development or aggravation of varicose veins requires adequate sample of patients and searching for interrelations. To date, the role of calcium in venous ulcers has been almost confirmed. Genetic analysis of varicose veins is important for understanding the pathology and selecting the most effective prevention, diagnostics and treatment. All this will further enable the fullest activation of all aspects of personalized medicine.

ЦЕЛЬ ИССЛЕДОВАНИЯ Изучение экспрессии связанных с ремоделированием актинового филамента генов ACTA1, PLXNA4 и SEMA3 в стенках варикозно измененных (ВВ) и неизмененных (НВ) вен у пациентов с разной протяженностью патологического рефлюкса в большой подкожной вене (БПВ). МАТЕРИАЛ И МЕТОДЫ Обследованы 26 пациентов, которых разделили на две равночисленные группы: с протяженностью патологического рефлюкса до нижней трети бедра (13 пациентов) и до нижней трети голени (13 пациентов). После выделения РНК из парных (ВВ и НВ, 26 пар) сегментов БПВ от каждого пациента методом ОТ-ПЦР в реальном времени была проведена оценка на уровне мРНК относительной экспрессии изучаемых генов. РЕЗУЛЬТАТЫ Показана разница в отношениях экспрессии (в ВВ к НВ внутри пар) гена ACTA1 между группами пациентов с разной протяженностью рефлюкса (p=0,03). Выявлена дифференциальная экспрессия гена PLXNA4 в ВВ в группе пациентов с протяженностью рефлюкса до нижней трети бедра (p=0,04), а также между подгруппами НВ от пациентов с протяженностью рефлюкса до нижней трети бедра и НВ от пациентов с рефлюксом до нижней трети голени (p=0,03). Показана дифференциальная экспрессия в ВВ (p=0,02) в группе пациентов с рефлюксом до нижней трети бедра для гена SEMA3A, продуктом которого является лиганд рецептора PLXNA4. ЗАКЛЮЧЕНИЕ Показана разница в экспрессии генов ACTA1, PLXNA4 и SEMA3, участвующих в процессах ремоделирования цитоскелета и, как следствие, венозной стенки, в образцах вен от пациентов с разной протяженностью патологического рефлюкса в БПВ. Таким образом, протяженность патологического рефлюкса в магистральной вене, определяющая вероятность рецидива рефлюкса после процедуры ASVAL, связана с ремоделированием стенки вены. Выявленные гены могут стать перспективными терапевтическими мишенями.

Background/Objectives: There is clear evidence for the higher prevalence of varicose veins (VVs) among women. In this regard, the research on sex differences affecting this condition is very important for sex-specific health care. We aimed to assess how male or female sex may contribute to the changes to gene expression profiles in the vein wall during varicose transformation. Methods: Paired varicose vein (VV) and non-varicose vein (NV) segments were harvested from patients with VVs after venous surgery. Processed RNAs from those samples were subjected to gene expression analysis by reverse transcription quantitative polymerase chain reaction (RT-qPCR) followed by further data analysis. Multiple linear regression (MLR) analysis was performed to identify and characterize relationships among multiple factors (relative mRNA levels of a gene in NV or VV or their ratio, as dependent variables) and sex (independent variable, used individually or in combination with other patient’s characteristics). For sex-specific gene regulation analysis, all potential binding sites for sex hormone receptors were identified in each gene’s regulatory region sequence. Results: Using the independent method and a replicative patient sample set, we validated our previous data on 23 genes’ differential expression in VVs and obtained insights on their sex-specific regulation. Sex (as an individual independent variable or in combination with other parameters—patient characteristics such as Age, BMI, CEAP class, Height, VVD manifestation and duration) was a moderate predictor (0.40 < R < 0.59; p (R) < 0.05) for the STK38L expression in VVs (with its higher mRNA level in NVs and VVs of women compared to men); sex was a strong predictor (0.6 < R < 0.79; p (R) < 0.05) for the TIMP1 expression in VVs (with its lower mRNA level in VVs of women compared to men); sex was a moderate predictor (0.40 < R < 0.59; p (R) < 0.05) for the EBF1 expression in NVs (with its lower mRNA level in NVs of women compared to men). Conclusions: Confirmed differential expression of the studied genes in VVs indicates their plausible participation in vein wall remodeling. Sex-specific expression in veins for the subset of those genes suggests their hormonal regulation as well as other mechanisms involved in VV pathogenesis. This work enriches our understanding of sex features for the development of VVs and may provide the foundation for future investigations and beneficial treatment options.

Varicose veins of the lower extremities is one of the most common diseases on Earth and its combination with other diseases is inevitable. The combination of diseases aggravates the course of each other. Rheumatoid arthritis worsens the course of varicose veins with trophic disorders – both independently – an increase in pro-inflammatory factors, a change in microcirculation, deformation of the limb axis with a violation of musculoskeletal function, and treatment of rheumatoid arthritis reduces the immune response of the body reducing the reparative capabilities of the body. Clinical case: a patient with a long course of rheumatoid arthritis and varicose veins. For a long time he used cytostatic drugs with a subsequent transition to hormonal drugs. For about 5 years, he noted the appearance of ulcers on both shins, which took a circular shape, which significantly reduced the quality of life and did not respond to conservative treatment. He repeatedly underwent inpatient treatment with intravenous administration of general restorative and vascular drugs. He was also constantly observed in the polyclinic at the place of residence with the implementation of local treatment of ulcerative surfaces. The patient was successively treated for varicose veins by endovenous laser coagulation of the trunks of large subcutaneous veins. The second stage was performed debridement of the wound surface and skin grafting with a free perforated flap. Between the stages, the appointment of drug therapy according to clinical recommendations. Rheumatoid arthritis and varicose veins aggravate each other, especially trophic manifestations. Treatment of such patients should be carried out by a team ofspecialists of various profiles together. Step-by-step treatment ofsuch patients with careful preparation for each of them shows excellent results. A special place is occupied by the patients’ commitment to treatment.