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

2016 ◽  
Vol 33 (1) ◽  
pp. 27-35 ◽  
Author(s):  
Alexandra S Shadrina ◽  
Mariya A Smetanina ◽  
Ekaterina A Sokolova ◽  
Darya V Shamovskaya ◽  
Kseniya S Sevost‘ianova ◽  
...  

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.

2016 ◽  
Vol 31 (9) ◽  
pp. 640-648 ◽  
Author(s):  
Alexandra S Shadrina ◽  
Mariya A Smetanina ◽  
Ekaterina A Sokolova ◽  
Kseniya S Sevost’ianova ◽  
Andrey I Shevela ◽  
...  

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.


2008 ◽  
Vol 23 (3) ◽  
pp. 137-141 ◽  
Author(s):  
M A Murphy ◽  
L Hands

Objectives Arteriovenous (AV) shunting has been postulated as the underlying cause of varicose veins. The aim of this study was to analyse pressure and oxygen content in primary varicose veins in order to determine evidence of arterial shunting. Methods Thirty-nine patients with varicose veins underwent cannulation of varicosities. The pressure and the blood oxygen content within varicosities were measured in different positions and during exercise. Similar measurements were made in the long saphenous veins of 10 control subjects without venous disease. Results Mean pressure in varicose veins in the supine position was 12.3 mmHg (Standard deviation [SD] 3.6 mmHg). Control subjects had similar pressures measured in the long saphenous vein. No pulsatile pressure tracings were obtained. Varicosity pressures in the erect position averaged 66 mmHg (SD 9 mmHg). In all cases, the pressure correlated with the distance of the varicosity from the heart. Pressure reduction in varicosities after exercise was significantly less than that in control subjects. Recovery time (RT 90) was also significantly shorter than in the control group. Mean venous pO2 in varicosities was 4.5 kPa (SD 1.0) in the supine position dropping to 3.9 kPa (SD 0.9) on standing; these values were not significantly different to samples from control subjects. Conclusions AV shunting is unlikely to be a causative factor in the development of primary varicose veins.


2020 ◽  
Vol 35 (7) ◽  
pp. 513-519 ◽  
Author(s):  
Yury Rusinovich ◽  
Volha Rusinovich

Aim This study examines the association between right heart diastolic function and clinical presentation of chronic venous disease and primary varicose veins of lower extremities. Material and methods We performed retrospective analysis of clinical, peripheral venous Duplex and tricuspid Doppler (early diastolic inflow E-wave, late diastolic inflow A-wave, ratios of E to A waves, early diastolic annular e′-wave, late diastolic annular a′-wave and systolic annular s′- wave) data of 85 patients, 133 legs with primary varicose veins. Results We found following significant (p-value < 0.05) associations between tricuspid Doppler and clinical presentation of chronic venous disease and primary varicose veins: Clinical Etiological Anatomical Pathophysiological clinical class influenced late diastolic inflow velocities (C6 class A-wave +11.2 cm/s or +27% in comparison with C2), late diastolic annular velocities (C6 class a′-wave +3.3 cm/s or +22% in comparison with C2), systolic annular velocities (C6 class s′-wave +3.7 cm/s or +27% in comparison with C2) and E/A ratios (C6 class E/A ratio −0.22 or −21% in comparison with C2). Recurrent varices in comparison with previously untreated are associated with significantly lower late diastolic inflow velocities (A-wave −4.4 cm/s or −9%) and preserved E/A ratios. Age significantly influenced tricuspid Doppler (E-, A-, e′-, a′-waves and E/A ratios) in patients with chronic venous disease. Conclusion Clinical presentation of primary varicose veins and chronic venous disease can be associated with the right heart diastolic function: C6 Clinical Etiological Anatomical Pathophysiological class in comparison with C2 is associated with increased right ventricular filling and impaired ventricular relaxation – right heart diastolic dysfunction; recurrent varices in comparison with previously untreated are associated with reduced right ventricular filling and preserved right heart diastolic function. Older age is the most important risk factor for varicose veins and chronic venous disease possible due to significant changes in right ventricular filling and in right heart diastolic function with age.


2011 ◽  
Vol 26 (suppl 2) ◽  
pp. 115-119 ◽  
Author(s):  
Nei Rodrigues Alves Dezotti ◽  
Edwaldo Edner Joviliano ◽  
Takachi Moriya ◽  
Carlos Eli Piccinato

CONTEXT: Previous studies have demonstrated improvement of venous hemodynamics after surgical treatment of primary varicose veins of the lower extremities using air plethysmography (APG). PURPOSE: To correlate the venous hemodynamics obtained by APG with the CEAP classification after surgical treatment of primary varicose veins. METHODS: We studied 63 limbs of 39 patients (35 women and 4 men) aged on average 46.3 years, operated upon at the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo, during the period from January 2001 to December 2004. The 63 limbs were divided into the three following groups according to CEAP classification: group C2 + C3 (38 limbs), group C4 (15 limbs) and group C5 + C6 (10 limbs). The patients were evaluated clinically before and 30 to 40 days after surgery by preoperative duplex ultrasonography and pre- and postoperative APG. RESULTS: There was an apparent hemodynamic improvement after surgical treatment of the varicose veins in the two groups of lower severity, but the improvement was significant in the most severe group based on venous filling index. CONCLUSION : Surgical treatment was beneficial for all three groups, but the greatest hemodynamic gain was observed in the group of highest clinical severity (group C5 + C6).


1996 ◽  
Vol 11 (3) ◽  
pp. 125-131 ◽  
Author(s):  
K. A. Myers ◽  
G. H. Zeng ◽  
R. W. Ziegenbein ◽  
P. G. Matthews

Objective: To use duplex ultrasound scanning to compare limbs with recurrent and primary varicose veins and to identify connections between deep veins and recurrences. Setting: A non-invasive vascular laboratory in Melbourne, Australia. Patients: A study of 779 limbs with recurrent varicose veins previously treated by ligation or stripping of the long saphenous vein and 1521 limbs with primary varicose veins. Main outcome measures: Connections between deep veins and recurrent varices, reflux in superficial and deep veins, and outward flow in perforators as demonstrated by duplex ultrasonography. Results: Recurrence was due to reflux in the long saphenous territory in 71.8%, short saphenous reflux alone in 14.7% or outward flow in calf perforators without saphenous reflux in 5.2%, while no source was detected in 8.3%. Limbs with recurrent veins in the long saphenous territory were compared with limbs with primary varicose veins; there was more frequent outward flow in thigh perforators (25.2% vs. 16.2%) but no difference for deep reflux (20.7% vs. 17.5%) or outward flow in calf perforators (56.8% vs. 53.1%). The source for recurrence in the long saphenous territory was from a single large connection in the groin in 46.3%, multiple smaller proximal connections in a further 46.3%, or thigh perforators in 7.4%. The destination was to an intact long saphenous vein in 33.7%, major tributaries in 28.7% or to other varices in 37.6%. Limbs known to have been treated by long saphenous ligation alone were compared with those known to be treated by long saphenous ligation and stripping; the source was more likely to be from a single large vein in the groin (60.3% vs. 39.9%) and the destination was more likely to be an intact long saphenous vein or major tributary (75.0% vs. 55.2%). Conclusions: Duplex ultrasound scanning detected the source of recurrent varicose veins in over 90% of patients and demonstrated whether there were single large or multiple smaller connections in the veins affected, and this helps to select the most appropriate treatment. Recurrence after stripping the long saphenous vein was more likely to be due to multiple small connections passing to scattered varices and this may allow more simple treatment by injection sclerotherapy rather than repeat surgery.


2016 ◽  
Vol 32 (9) ◽  
pp. 601-607 ◽  
Author(s):  
Igor A Zolotukhin ◽  
Evgeny I Seliverstov ◽  
Elena A Zakharova ◽  
Alexander I Kirienko

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.


2020 ◽  
Vol 9 (5) ◽  
pp. 1251 ◽  
Author(s):  
Daniel P. Zalewski ◽  
Karol P. Ruszel ◽  
Andrzej Stępniewski ◽  
Dariusz Gałkowski ◽  
Jacek Bogucki ◽  
...  

Chronic venous disease (CVD) is a vascular disease of lower limbs with high prevalence worldwide. Pathologic features include varicose veins, venous valves dysfunction and skin ulceration resulting from dysfunction of cell proliferation, apoptosis and angiogenesis. These processes are partly regulated by microRNA (miRNA)-dependent modulation of gene expression, pointing to miRNA as a potentially important target in diagnosis and therapy of CVD progression. The aim of the study was to analyze alterations of miRNA and gene expression in CVD, as well as to identify miRNA-mediated changes in gene expression and their potential link to CVD development. Using next generation sequencing, miRNA and gene expression profiles in peripheral blood mononuclear cells of subjects with CVD in relation to healthy controls were studied. Thirty-one miRNAs and 62 genes were recognized as potential biomarkers of CVD using DESeq2, Uninformative Variable Elimination by Partial Least Squares (UVE-PLS) and ROC (Receiver Operating Characteristics) methods. Regulatory interactions between potential biomarker miRNAs and genes were projected. Functional analysis of microRNA-regulated genes revealed terms closely related to cardiovascular diseases and risk factors. The study shed new light on miRNA-dependent regulatory mechanisms involved in the pathology of CVD. MicroRNAs and genes proposed as CVD biomarkers may be used to develop new diagnostic and therapeutic methods.


2021 ◽  
Vol 10 (15) ◽  
pp. 3239
Author(s):  
Miguel A. Ortega ◽  
Oscar Fraile-Martínez ◽  
Cielo García-Montero ◽  
Miguel A. Álvarez-Mon ◽  
Chen Chaowen ◽  
...  

Chronic venous disease (CVD) is a multifactorial condition affecting an important percentage of the global population. It ranges from mild clinical signs, such as telangiectasias or reticular veins, to severe manifestations, such as venous ulcerations. However, varicose veins (VVs) are the most common manifestation of CVD. The explicit mechanisms of the disease are not well-understood. It seems that genetics and a plethora of environmental agents play an important role in the development and progression of CVD. The exposure to these factors leads to altered hemodynamics of the venous system, described as ambulatory venous hypertension, therefore promoting microcirculatory changes, inflammatory responses, hypoxia, venous wall remodeling, and epigenetic variations, even with important systemic implications. Thus, a proper clinical management of patients with CVD is essential to prevent potential harms of the disease, which also entails a significant loss of the quality of life in these individuals. Hence, the aim of the present review is to collect the current knowledge of CVD, including its epidemiology, etiology, and risk factors, but emphasizing the pathophysiology and medical care of these patients, including clinical manifestations, diagnosis, and treatments. Furthermore, future directions will also be covered in this work in order to provide potential fields to explore in the context of CVD.


Vascular ◽  
2021 ◽  
pp. 170853812110128
Author(s):  
Dominic Mühlberger ◽  
Anne-Katrin Zumholz ◽  
Erich Brenner ◽  
Achim Mumme ◽  
Markus Stücker ◽  
...  

Objectives Cellular senescence could play a role in the development of venous disease. Superficial venous reflux at the saphenofemoral junction is a common finding in patients with primary varicose veins. Furthermore, reflux in this essential area is associated with higher clinical stages of the disease and recurrent varicose veins. Therefore, this pilot study aimed to investigate cellular senescence in the immediate area of the saphenofemoral junction in patients with healthy veins, primary varicose veins and additionally in patients with recurrent varicose veins due to a left venous stump. Methods We analyzed vein specimens of the great saphenous vein immediately at the saphenofemoral junction. Healthy veins were collected from patients who underwent arterial bypass reconstructions. Samples with superficial venous reflux derived from patients who received high ligation and stripping or redo-surgery at the groin, respectively. Sections were stained for p53, p21, and p16 as markers for cellular senescence and Ki67 as a proliferation marker. Results A total of 30 samples were examined (10 healthy, 10 primary varicose, and 10 recurrent varicose veins). We detected 2.10% p53+ nuclei in the healthy vein group, 3.12% in the primary varicose vein group and 1.53% in the recurrent varicose vein group, respectively. These differences were statistically significant ( p = 0.021). In the healthy vein group, we found 0.43% p16+ nuclei. In the primary varicose vein group, we found 0.34% p16+ nuclei, and in the recurrent varicose vein group, we found 0.74% p16+ nuclei. At the p < 0.05 level, the three groups tended to be significant without reaching statistical significance ( p = 0.085). There was no difference in respect of p21 and Ki67. Conclusion We found significantly higher expression rates of p53 in primary varicose veins at the saphenofemoral junction than in healthy veins. p16 expression tended to be increased in the recurrent varicose vein group. These preliminary findings indicate that cellular senescence may have an impact in the development of varicose veins or recurrence. Further studies addressing this issue are necessary.


2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Ewa Grudzińska ◽  
Andrzej Lekstan ◽  
Ewelina Szliszka ◽  
Zenon P. Czuba

The pathogenesis of chronic venous disease (CVD) remains unclear, but lately inflammation is suggested to have an important role in its development. This study is aimed at assessing cytokines released by lymphocytes in patients with great saphenous vein (GSV) incompetence. In 34 patients exhibiting oscillatory flow (reflux) in GSV, blood was derived from the cubital vein and from the incompetent sapheno-femoral junction. In 12 healthy controls, blood was derived from the cubital vein. Lymphocyte culture with and without stimulation by phytohemagglutinin (PHA) was performed. Interleukins (IL) 1β, 2, 4, 10, 12 (p70), and 17A; interleukin 1 receptor α (IL-1ra); tumor necrosis factor-α (TNF-α); interferon-gamma (IFN-γ); and RANTES were assessed in culture supernatants by the Bio-Plex assay. In both stimulated and unstimulated samples, in the examined group, IL-1β and IFN-γ had higher concentrations and RANTES had lower concentrations when compared to those in the control group. In the examined group, IL-4 and IL-17A had higher concentrations without stimulation and TNF-α had higher concentrations with stimulation. The GSV samples had higher IL-2, IL-4, IL-12 (p70), and IFN-γ concentrations without stimulation and lower IL-2 and TNF-α concentrations with stimulation when compared to those of the upper limb in the examined group. These observations indicate that the oscillatory flow present in incompetent veins causes changes in the cytokine production by lymphocytes, promoting a proinflammatory profile. However, the relations between immunological cells, cytokines, and the endothelium require more insight.


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