Daily Duration of Compression Treatment in Chronic Venous Disease Patients: A Systematic Review.

Background: There are no data on the daily regimen of compression therapy in patients with chronic venous disease. This systematic review aimed to establish the optimal daily duration of compression treatment. Methods: A systematic search of CENTRAL and MEDLINE was performed to identify RCTs, non-RCTs, reviews, systematic reviews, meta-analyses, and guidelines evaluating the use of compression regimens in the treatment of varicose veins. Results: Thirty-two RCTs, three non-RCTs, four observational studies, and two crossover trials reporting the duration and regimes of compression treatment fulfilled the inclusion criteria. The daily duration of compression was reported in patients after invasive treatment, for venous ulcer treatment, in patients with venous symptoms. The quality of the studies varied. We could not conduct a meta-analysis due to the heterogeneity of the research data and their quality. Twenty-three studies reported results of compression usage after invasive procedures. Eight studies reported daily duration regimens in patients with venous ulcers. Nine studies reported the impact of compression on venous symptoms and/or edema or limb volume change. One study was conducted to assess if compression improves QoL in venous patients. While there was a clear difference found in the daily duration depending on the clinical scenario, no data in support of exact regimens were found. Conclusions: There are no reliable data supporting exact daily regimens of compression treatment in various cohorts of CVD patients.

Monocyte chemoattractant protein 1 plasma concentration in blood from varicose veins decreases under venoactive drug treatment.

BACKGROUND: Vein-specific inflammation leads to vascular smooth muscle cells proliferation and extracellular matrix degradation of vein wall. This process is known as remodeling and is promoted by "trapped" leukocytes. Monocyte chemoattractant protein 1 (MCP-1) is a chemokine responsible for trafficking of leukocytes from blood to vein wall. The aim of this study was to measure the MCP-1 concentration in varicose veins blood before and after venoactive drug therapy and to compare it with a concentration of blood from varicose veins of subjects who did not receive drug treatment. METHODS: Non-randomized comparative study was conducted on 30 patients with primary varicose veins. 20 patients of the study group received diosmin 900 mg/hesperidin 100 mg once daily. 10 controls received no treatment. MCP-1 level was measured (pg/mL) in the blood from varicose veins twice, at the day of inclusion and after 60 days. Legs discomfort related to chronic venous disease (CVD) symptoms was measured with 10-cm Visual Analogue Scale (VAS) at inclusion and at completion of the study. RESULTS: Median (interquartile range, IQR) MCP-1 concentrations in treatment and control groups at inclusion were 171.9 (124.4-216.0) and 157.0 (120.1-163.1), resp., P=0.285. After 60 days of treatment MCP-1 level decreased, but non-significantly to 152.3 (124.1-178.3). In patients who did not receive treatment chemokine level slightly increased to 163.0 (134.0-172.9). Median changes over time were -6.6 (-30.9-7.4) and 10.6 (-3.7-19.2) in the study and control groups, resp. (P=0.048). After 60 days in 12 of 19 and 2 of 9 patients of treatments and control groups MCP-1 decreased (P=0.103). Odds ratio for MCP-1 decreasing was 9.5 (95% CI 1.1-81.5, P=0.043) for those who received venoactive drug. Mean (± standard deviation [SD]) legs discomfort significantly dropped in the study group from 5.7 (±2.5) to 1.9 (±2.2) (P=0.0003), while in controls no changes were registered: 3.4 (±1.3) and 3.5 (± 1.4), resp., P=0.28). Mean difference of VAS at baseline and at follow-up was -3.5 (±2.6) and 0.9 (±2.1), resp. (P<0.0001). CONCLUSIONS: Plasma concentration of MCP-1 in varicose veins blood demonstrates a tendency to decrease under two months treatment with a venoactive drug. Future studies are needed to reveal a possible role of MCP-1 as a target considering its role in varicose veins pathogenesis.

Quantitative and structural characteristics of mitochondrial DNA in varicose veins.

OBJECTIVE: We examined quantitative (in terms of mtDNA/nuclear DNA) and structural (in terms of common deletions in the MT-ND4 gene region) characteristics of mitochondrial DNA (mtDNA) in varicose veins (VVs) and venous wall layers by comparing mitochondrial genome parameters, as well as mitochondrial function (in terms of mitochondrial membrane potential (MtMP)), in varicose vein (VV) vs. non-varicose vein (NV) tissue samples. METHODS: We analyzed paired great saphenous vein samples (VV vs. NV segments from each patient left after venous surgery) harvested from patients with VVs. Relative mtDNA level and the proportion of no-deletion mtDNA were determined by a multiplex quantitative PCR (qPCR), confirming the latter with a more sensitive method - droplet digital PCR (ddPCR). Mitochondria's functional state in VVs was assessed using fluorescent (dependent on MtMP) live-staining of mitochondria in venous tissues. RESULTS: Total mtDNA level was lower in VV than in NV samples (predominantly in the t. media layer). ddPCR analysis showed lower proportion of no-deletion mtDNA in VVs. Because of the decrease in relative MtMP in VVs, our results suggest a possible reduction of mitochondrial function in VVs. CONCLUSION: Quantitative and structural changes (copy number and integrity) of mtDNA are plausibly involved in VV pathogenesis. Future clinical studies implementing the mitochondrial targeting may be eventually fostered after auxiliary mechanistic studies.

Artificial Intelligence Evidence-Based Current Status and Potential for Lower Limb Vascular Management.

Consultation prioritization is fundamental in optimal healthcare management and its performance can be helped by artificial intelligence (AI)-dedicated software and by digital medicine in general. The need for remote consultation has been demonstrated not only in the pandemic-induced lock-down but also in rurality conditions for which access to health centers is constantly limited. The term "AI" indicates the use of a computer to simulate human intellectual behavior with minimal human intervention. AI is based on a "machine learning" process or on an artificial neural network. AI provides accurate diagnostic algorithms and personalized treatments in many fields, including oncology, ophthalmology, traumatology, and dermatology. AI can help vascular specialists in diagnostics of peripheral artery disease, cerebrovascular disease, and deep vein thrombosis by analyzing contrast-enhanced magnetic resonance imaging or ultrasound data and in diagnostics of pulmonary embolism on multi-slice computed angiograms. Automatic methods based on AI may be applied to detect the presence and determine the clinical class of chronic venous disease. Nevertheless, data on using AI in this field are still scarce. In this narrative review, the authors discuss available data on AI implementation in arterial and venous disease diagnostics and care.

The Effect of Venoactive Drug Therapy on the Development and Severity of Post-Embolization Syndrome in Endovascular Interventions on the Gonadal Veins.

Objective. To evaluate the incidence of post-embolization syndrome (PES) and the effect of venoactive therapy on its development, severity, and duration after endovascular embolization of gonadal veins (EEGV) with coils in patients with pelvic congestion syndrome (PCS). Materials and Methods. We analyzed the outcomes of EEGV with coils in 70 female patients who received (n = 38; group 1) or did not receive (n = 32; group 2) treatment with a venoactive drug (VAD) before and after the procedure. Assessments of the EEGV efficacy and for possible signs of PES were done on days 1, 5, 10, 15, 20, and 30 after the intervention. All patients underwent transvaginal and transabdominal duplex ultrasound scanning (DUS) after EEGV. In addition, patients with PES were examined using the computed tomography of the pelvic veins in the postprocedural period. Results. Technical success of EEGV was achieved in 100% of patients. Pelvic venous pain (PVP) reduction after EEGV was observed in 77.1% of patients. The PES was diagnosed in 18.6% of cases (10.5% in group 1 vs. 28.1% in group 2, p > 0.05). In three patients of group 1, the protrusion of coils was suspected and eventually verified during the resection of the left gonadal vein with coils. The group 1 patients had less severe post-embolization pain (6.2 ± 0.4 vs. 7.8 ± 0.3 scores in group 2; p = 0.009) and three times shorter duration of PES (5.0 ± 1.2 vs. 16.2 ± 2.7 days; p = 0.003). No significant differences in the diameters of gonadal veins, side of embolization, and number of coils were revealed between patients with and without PES. The rate of parametrium vein thrombosis was found to be significantly higher in patients with PES than in those without PES (30.7% vs. 18.5%, respectively; p < 0.05). Conclusion. The PES is a frequent complication of EEGV with coils and occurs in 18.6% of patients. Venoactive treatment does not effect the incidence of this complication but reduces the PES severity and duration.

A randomized trial of class II compression sleeves for full legs versus stockings after thermal ablation with phlebectomy.

OBJECTIVE: Compression stockings and bandages are widely used after invasive treatment of varicose veins. The goals of compression after venous interventions are to reduce pain, bruising, and ecchymosis. Nevertheless, patients often report discomfort with the compression. To make postprocedural compression more tolerable, foot-sparing bandages were tested in a randomized clinical trial of noninferiority. METHODS: A total of 187 patients were randomized to use class II foot-sparing compression sleeves for the full leg or class II stockings after radiofrequency ablation with concomitant phlebectomy. The primary endpoint was the quality of life, measured using the Chronic Venous Disease Quality of Life Questionnaire 20-item scale 30 days after intervention. The secondary endpoints were pain in the leg and discomfort related to the compression garment, which were assessed using the visual analog scale (VAS) at 2, 7, 14, and 30 days. RESULTS: The global index score of the questionnaire was 66.1 and 70.6 and 83.8 and 87.7 for the sleeve and stocking groups before and 30 days after intervention, respectively (P = .542 and P = .150, respectively). The VAS for pain score in the operated leg was slightly higher in the sleeve group the day after the intervention (score, 2.1 vs 1.6; P = .03). At 7, 14, and 30 days, the VAS for pain scores did not differ significantly (score, 0.7 vs 0.5; 0.5 vs 0.3; and 0.1 vs 0.1, respectively; P = NS for all). The VAS for discomfort score was not significantly different statistically in the study group at 2 days (sleeve, 1.9; vs stocking, 1.4; P = .08) but was higher after 7 days (sleeve, 0.9; vs stocking, 0.6; P = .008). No difference in discomfort was found between the study and control groups at 14 or 30 days (sleeve, 0.6; vs stocking, 0.4; and sleeve, 0.4; vs stocking, 0.4, respectively; P = NS for both). CONCLUSIONS: Quality of life after thermal ablation with phlebectomy improved equivalently in patients who had used class II compression sleeves for full legs and those who had used class II compression stockings. Pain and discomfort were slightly higher in the sleeve group.

Inferior vena cava filters utilization in patients with venous thromboembolism: Analysis of a database of a tertiary hospital.

PURPOSE: The aim of the study was to assess the inferior vena cava filter (IVCF) utilization in patients with venous thromboembolism (VTE) in tertiary care. METHODS: We performed a retrospective analysis of database of a tertiary hospital in 2016-2017. All the records of patients admitted for VTE or diagnosed with VTE being hospitalized for other reasons were extracted. The data collected were number of patients, who received IVCF, indications to filter insertion, PE and death rate after procedure, frequency of IVCF occlusion. RESULTS: 2399 patients with VTE were admitted to hospital. 442 (18,4%) of them received IVCF (239 in 2016 and 203 in 2017). Retrievable models were used in most cases (98,8%). In 119 (5,0%) patients cava filters were used due to contraindications for anticoagulation, while in 184 (7,7%) patients' anticoagulation was not effective and thrombosis progression was registered. 101 (4,2%) patients received IVCF due to high PE risk (length of floating thrombus ≥7 cm, in proximal location), high pulmonary hypertension was indication to IVCF insertion in 38 (1,6%) patients with deep vein thrombosis (DVT) in combination with pulmonary embolism (PE). Overall mortality rate after IVCF insertion was 5 (0,2%). No fatal PE was registered. IVCF occlusion during hospitalization occurred in 116 (4,8%) cases. Only 29 (1,2%) of patients were admitted back for IVCF removal. CONCLUSIONS: Every one in five patients with proximal DVT and/or PE receives IVCF in a routine practice in tertiary hospital. The most common indications for IVCF implantation were inability for anticoagulation or anticoagulation failure. Removal rate of retrievable cava filters is low.

Risk factors for venous symptoms in Russian patients with chronic venous disease.

Objectives: The study aimed to investigate risk factors for venous symptoms in Russian patients with chronic venous disease (CVD).Methods: Data on 487 patients with CVD aged 18 years and more were extracted from the database of a cross-sectional population-based study on the prevalence of CVD in a rural settlement. Risk factors for venous symptoms were calculated by multiple regression analysis. The study is registered at clinicaltrials.gov as NCT03900234, 1 April 2019.Results: A total of 259 patients (53.2%) had venous symptoms. Female gender, hard labour (HRs 1.8 and 1.4, p < .01), age, family history of CVD and being employed (HRs 1.009, 1.3, 1.27, p < .05) are risk factors for development of symptoms. After calculating for different complaints separately, female gender was confirmed as a risk factor for all symptoms. Family history of CVD with HR 1.4 is a risk factor for heaviness (p < .01) and fatigue (p < 0.05). Employment predicts heaviness, sensation of swelling and night cramps - HRs 1.38, 1.7 and 1.9 respectively (p < .05). Hard labour is a risk factor for sensation of swelling with HR 2.1 (p < .05), pain and night cramps (HRs 2.2 and 4.4, p < .01). Prolonged standing is associated with sensation of swelling - HR 1.05 (p < .05). Superficial venous reflux is a predictor only for venous pain (HR 2.4, p < .01).Conclusions: This study presents independent risk factors for venous symptoms in CVD patients. It demonstrates that different symptoms are associated with different factors.

DNA methylation and gene expression profiling reveal MFAP5 as a regulatory driver of extracellular matrix remodeling in varicose vein disease.

AIM: To integrate transcriptomic and DNA-methylomic measurements on varicose versus normal veins using a systems biological analysis to shed light on the interplay between genetic and epigenetic factors. MATERIALS & METHODS: Differential expression and methylation were measured using microarrays, supported by real-time quantitative PCR and immunohistochemistry confirmation for relevant gene products. A systems biological 'upstream analysis' was further applied. RESULTS: We identified several potential key players contributing to extracellular matrix remodeling in varicose veins. Specifically, our analysis suggests MFAP5 acting as a master regulator, upstream of integrins, of the cellular network affecting the varicose vein condition. Possible mechanism and pathogenic model were outlined. CONCLUSION: A coherent model proposed incorporates the relevant signaling networks and will hopefully aid further studies on varicose vein pathogenesis.

Genome-wide association study in ethnic Russians suggests an association of the MHC class III genomic region with the risk of primary varicose veins.

Heredity is a well-known risk factor for varicose veins, but genetic basis of this condition remains poorly studied. Our aim was to conduct a large-scale genetic association study for primary varicose veins (PVVs) in the population of ethnic Russians. An initial scan using Illumina HumanExome-12 v1.0 BeadChip was performed for 273 patients with PVVs and 250 controls without a history of chronic venous disease and other venous disorders. After quality control and removal of monomorphic markers, 25,424 common and 48,232 rare variants were included in the analysis. 42 single nucleotide polymorphisms (SNPs) were genotyped in the independent replication cohort of 447 PVVs patients and 443 controls. Association of common variants with PVVs was investigated by logistic regression, and the impact of rare variants was analyzed using sequence kernel association test. No effect of low frequency alleles has been revealed in our study. Common variant analysis identified a promising signal at chromosome 6 within classical major histocompatibility complex (MHC) class III subregion. The most strongly associated SNP in a combined analysis that reached a suggestive significance level of 3.2e-05 was polymorphism rs4151657 in the complement factor B gene. Testing for potential pleiotropy with other traits indicated that the same causal variant in this region increases the risk of rheumatoid arthritis and has a negative impact on human height. Our results provide suggestive evidence for the involvement of the MHC class III genes in the pathogenesis of PVVs. Further independent studies are needed to confirm our pilot findings.

Allele rs2010963 C of the VEGFA gene is associated with the decreased risk of primary varicose veins in ethnic Russians.

Objective To study the association of polymorphisms rs699947, rs2010963, rs3025039 in the VEGFA gene region and rs1870377, rs2305949, rs2071559 in the VEGFR2 gene region with the risk of primary varicose veins in ethnic Russians. Methods Genotypes were determined by real-time PCR allelic discrimination. The case group consisted of 448 patients with primary varicose veins and the control group comprised 609 individuals without a history of chronic venous disease. Association was studied by logistic regression analysis. Results Allele rs2010963 C was associated with the decreased risk of varicose veins (additive model of inheritance: odds ratio = 0.73, 95% confidence interval = 0.59-0.91, P = 0.004). Conclusions Our results provide evidence that polymorphism rs2010963 located in the 5' untranslated region of the VEGFA gene can influence genetic susceptibility to primary varicose veins in Russians. Otherwise, it can be in linkage disequilibrium with another functional single nucleotide polymorphism that can alter the level of vascular endothelial growth factor A protein.

Polymorphisms in inflammation-related genes and the risk of primary varicose veins in ethnic Russians.

Inflammation was shown to be activated in varicose veins, although its role in the development of vein wall transformation remains inconclusive. We aimed to investigate the influence of 13 inflammation-related single nucleotide polymorphisms (SNPs) TNF rs1800629 and rs3093661, IL1A rs1800587, IL1RN rs4251961, IL6 rs1800795 and rs1800796, IFNG rs2430561, IL10 rs1800896, TGFB1 rs1800469, HIF1A rs11549465, NFKB1 rs28362491, and rs4648068 on the risk of primary varicose veins (PVVs) in ethnic Russians. We genotyped 709 patients with PVVs and 278 individuals without a history of chronic venous disease and performed a single SNP and a haplotype analysis. Several associations with P < 0.05 were revealed in our study. Variant allele HIF1A rs11549465 T, TNF rs3093661 A, and NFKB1 rs28362491 ATTG deletion showed the reverse association with PVV risk, and allele IL6 rs1800795 C was associated with the increased risk of the studied pathology. Haplotype analysis revealed associations of TNF haplotypes rs3093661 A-rs1800629 G and IL6 rs1800795 C-rs1800796 G with the decreased and the increased risk of PVVs, correspondingly. However, all the observed associations failed to reach statistical significance after the correction for multiple testing, which was set at a level of 10-3 due to many tests performed. Our study therefore provides evidence that investigated polymorphisms do not play a major role in susceptibility to PVVs.

Prevalence and Risk Factors for Chronic Venous Disease in the General Russian Population.

OBJECTIVE/BACKGROUND: The aim was to establish the prevalence of chronic venous disease (CVD) and its risk factors in the general population. METHODS: This was a population based, cross sectional study. In total, 703 residents aged > 18 years from the rural community of Kryukovo (Central Russia) were enrolled. Medical history was taken and clinical examination performed, documenting venous signs/symptoms. The CEAP classification of the most affected limb was used. Duplex ultrasound was performed to register morphological changes and reflux in deep and superficial veins. RESULTS: There were 63% women and 37% men (mean age 53.5 years). CVD was found in 69.3%. Of all participants 4.7% were C0S and 34.3% were C1. Chronic venous insufficiency (C3-C6) was found in 8.2% and venous ulcers (C5-C6) in 1.1%. Venous pain, heaviness, fatigue, itching, and the sensation of swelling were documented in 14.8%, 36.3%, 32.8%, 7.0% and 29.1% of patients respectively. Family history was the significant risk factor for both CVD (hazard ratio [HR] 1.3) and primary varicose vein disease (HR 1.6; p < .01). Female sex was a risk factor only for CVD (HR 1.3; p < .01) but not for varicose veins. Age was a risk factor for CVD (HR 1.01) and for varicose veins (HR 1.02; p < .01). For women, number of births (HR 1.05; p < .05) and menopause (HR 1.3; p < .01) were risk factors for CVD. Menopause was a risk factor for varicose veins (HR 2.0; p < .05). CONCLUSION: This study provides data on the prevalence of CVD, venous abnormalities and risk factors in Russia. The results contribute to already established data, giving a more complete outlook on the global prevalence of CVD.

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

OBJECTIVE: Monocyte chemoattractant protein 1 (MCP-1) is a chemokine responsible for monocyte, basophil, and T-lymphocyte attraction. Polymorphism rs1024611 located in the regulatory region of the MCP1 gene has previously been shown to be associated with increased MCP-1 production. In our study, we aimed to examine the association of rs1024611 with the risk of primary varicose veins (PVVs) of lower extremities. METHODS: The case group comprised 470 patients with PVVs, and the control group included 269 individuals without a history of chronic venous disease. All cases and controls were ethnic Russians. Genotypes were determined by real-time polymerase chain reaction allelic discrimination. Association was studied by logistic regression analysis. RESULTS: We revealed the association of genotype G/G with the increased risk of PVVs (odds ratio [OR], 1.87; 95% confidence interval [CI], 1.02-3.44; P = .04). In the subgroup analysis, association was revealed only in patients with C2 Clinical, Etiology, Anatomy, and Pathophysiology class (allele G: OR, 1.62 [95% CI, 1.13-2.33; P = .008]; genotype G/G: OR, 3.22 [95% CI, 1.43-7.27; P = .005]), in patients with age at onset of PVVs before 30 years (allele G: OR, 1.41 [95% CI, 1.08-1.85; P = .01]; genotype G/G: OR, 2.35 [95% CI, 1.22-4.55; P = .01]), and in patients who declared no family history (allele G: OR, 1.46 [95% CI, 1.02-2.09; P = .04]; genotype G/G: OR, 2.50 [95% CI, 1.11-5.63; P = .03]). CONCLUSIONS: Our results provide evidence for MCP-1 involvement in the development of PVVs and indicate that inflammation could be implicated in the pathogenesis of this condition.

Short-term results of isolated phlebectomy with preservation of incompetent great saphenous vein (ASVAL procedure) in primary varicose veins disease.

Objective To establish an effect of isolated phlebectomy in patients with incompetent great saphenous vein (Ambulatory Selective Varices Ablation under Local anesthesia (ASVAL) procedure) on the reflux and diameter of the trunk and to assess recurrence rate of varicose veins at one year. Material and methods We conducted a prospective study on patients with primary varicose veins and with C2 or C2,3 or C2,3,4 or C2,4 classes of chronic venous disease and great saphenous vein incompetence. The study included 67 patients (51 women and 16 men; 75 limbs in total). Age varied from 17 to 71 years; mean age was 46.8 years (SD 13.9). We recorded the presence or absence of reflux in the great saphenous vein with duplex ultrasound before and after surgery. The recurrence of varicose veins was evaluated at 12 months. All the patients underwent isolated phlebectomy with preservation of incompetent great saphenous vein (ASVAL procedure) under local anesthesia. Results At one year after removing of tributaries of the incompetent trunk, 66% of them were competent. Reflux persisted in 17% of great saphenous veins with reflux above mid-thigh and in 61% of trunks with reflux extended below the mid-thigh (p = 0.0004). The diameter of all the veins decreased significantly no matter reflux disappeared or not. Varicose veins reoccurred in 13.5% cases. In 6.5% of limbs with a reflux above the mid-thigh, the recurrence was registered at one year, while in the limbs with the reflux below the mid-thigh at a baseline, the recurrence rate was 25% (p = 0.036). Conclusion Isolated phlebectomy with a preservation of incompetent great saphenous vein leads to disappearance of reflux in a majority of cases and to significant decrease of vein diameter in all the cases. ASVAL procedure could be considered as a less aggressive and less expensive approach in selected cases. Clear indications for isolated phlebectomy need to be established.

Allele and genotype frequencies of polymorphisms in cytokine genes in ethnic Russian individuals from Moscow, Russia.

Two hundred and twenty eight ethnic Russian individuals from Moscow, Russia, were genotyped at 14 single nucleotide polymorphisms CCL2 A-2578G; VEGFA C-2578A, G-634C, and C+936T; TNF G+419A and G-308A; IL1A G-889A; IL1RN T+1018C; IL6G-174C and G-572C; IFNG T+874A; IL1B C-511T; IL10 A+1082G; TGFB1 C-509T. Genotypes were determined using real-time polymerase chain reaction with TaqMan probes and polymerase chain reaction followed by melting analysis of dual-labeled probe. Genotype distribution was in accordance with Hardy-Weinberg equilibrium for all studied polymorphisms. Genotype data are available in the Allele Frequencies Net Database under identifier AFND 3367 and the population name "Russia Moscow Cytokine".

Polymorphisms in the MTHFR and MTR genes and the risk of varicose veins in ethnical Russians.

OBJECTIVES: The objective of this study was to study the association of polymorphisms MTHFR C677T (rs1801133) and MTR A2756G (rs1805087) with the risk of varicose veins in ethnical Russians. METHODS: We genotyped 475 patients with varicose veins, 168 individual without chronic venous disease, and the population-based group of 896 subjects. Association was studied using logistic regression analysis adopting co-dominant, additive, recessive, and dominant models of inheritance. RESULTS: None of the polymorphisms showed a statistically significant association with the risk of varicose veins. CONCLUSIONS: Our results provide evidence that the studied polymorphisms do not contribute to genetic susceptibility to varicose veins in ethnical Russians.

HFE p.C282Y gene variant is associated with varicose veins in Russian population.

Recently, the association of polymorphism rs1800562 (p.C282Y) in the hemochromatosis (HFE) gene with the increased risk of venous ulceration was shown. We hypothesized that HFE gene polymorphism might be involved not only in ulceration process, but also in susceptibility to primary varicose veins. We genotyped HFE p.C282Y (rs1800562) and p.H63D (rs1799945) variants in patients with primary varicose veins (n = 463) and in the control group (n = 754). In our study, p.282Y variant (rs1800562 A allele) was significantly associated with the risk of varicose veins (OR 1.79, 95 % CI = 1.11-2.89, P = 0.02). A borderline significant reverse association of p.63D variant (rs1799945 G allele) with venous leg ulcer development was revealed in Russians (OR 0.25, 95 % CI = 0.06-1.00, P = 0.05), but not in the meta-analysis (P = 0.56). We conclude that the HFE gene polymorphism can affect the risk of developing primary varicose veins.

Association of polymorphisms near the FOXC2 gene with the risk of varicose veins in ethnic Russians.

OBJECTIVE: To investigate the association of polymorphisms located near the FOXC2 gene with the risk of varicose veins in ethnic Russians. METHODS: Allele, genotype, and haplotype frequencies were determined in the sample of 474 patients with primary varicose veins and in the control group of 478 individuals without a history of chronic venous disease. RESULTS: Polymorphisms rs7189489, rs4633732, and rs1035550 showed the association with the increased risk of varicose veins, but none of the observed associations remained significant after correction for multiple testing. Haplotype analysis revealed the association of haplotype rs7189489 C-rs4633732 T-rs34221221 C-rs1035550 C-rs34152738 T-rs12711457 G with the increased risk of varicose veins (OR = 2.67, P = 0.01). CONCLUSIONS: Our results provide evidence that the studied polymorphisms do not play a major role in susceptibility to varicose veins development in the Russian population.