Vascular Endothelial Growth Factor Gene Polymorphisms Research Articles

Vascular Endothelial Growth Factor (VEGF) and Its Role in the Progression and Development of Breast Tumor

Breast cancer is the most common type of cancer in women and is widely known. Angiogenesis is the process through which new blood vessels develop from the body's current vascular system. It is essential for tumor growth, invasiveness, and metastasis, and so plays a pivotal role in the development of carcinoma. Proteolytic and proangiogenic catalyst activators and inhibitors regulate angiogenesis in a hierarchical fashion. The angiogenic process is largely under the direction of VEGF. In a select number of malignant tumors, the VEGF gene is overexpressed. The function of VEGF in angiogenesis has been the subject of intensive study in recent years. In breast cancer patients, VEGF plasma levels are highly predictive of tumor growth and survival. Several VEGF gene polymorphisms, have been identified to affect gene expression level in prior investigations. Epidemiological studies have linked polymorphisms in the VEGF gene to altered cancer risk, tumor growth, and metastasis. Previous research on VEGF polymorphism to evaluate the association between genes and breast cancer susceptibility was scant. The current review discusses the role of VEGF in the progression of breast cancer in addition to its promising usage as a predictive marker for breast cancer.

VEGF gene polymorphisms in Iranian patients with intracranial glioblastoma.

Glioblastoma is one of the most common malignant brain tumors in adults with poor prognosis. Neovascularization is one of the characteristics of these tumors, which is associated with overexpression of vascular endothelial growth factor (VEGF). Accordingly, single nucleotide polymorphisms of this gene could play an important role in structural and functional alterations leading to overexpression of this gene in GBM. A total number of 49 patients with GBM and 50 healthy controls were included in the current study. The Genomic DNA was extracted from brain tumor/tissue samples, and after purification assessment, the alleles, and genotypes of rs3025039 and rs2010963 polymorphisms of the VEGF gene were investigated using T-ARMS-PCR. The "T" allele of rs3025039 was 2.79 times more frequent in GBM patients compared to controls (P=0.01). Moreover, the "CT" genotype was 2.83 times more common among patients (P=0.015), while the "CC" was more frequent in controls (P=0.009). The mean overall survival was significantly different between three genotypes of rs3025039, with the longest survival time in "CT" genotype (15.10±5.21, P=0.041). Besides, rs2010963, was significantly associated with GBM occurrence, with the "G" allele being 1.96 times more frequent in patients (P=0.01), as well as the "GG" genotype, which was 7.87 times more common in patients (P<0.001). Polymorphisms of VEGF could potentially play a role in pathogenesis of GBM, as the allele and genotype distributions of rs3025039 and rs2010963 SNPs were significantly associated with GBM occurrence.

Genetic Polymorphism in Patients with Diabetic Nephropathy and Retinopathy: A Cross-sectional Study

Introduction: The chronic persistence of diabetes leads to microvascular complications, such as Diabetic Nephropathy (DN) and Diabetic Retinopathy (DR). Both of these are progressive disorders involving pathological changes in capillaries. A few biochemical pathways have been suggested to link hyperglycaemia and microvascular complications. The probability of developing and progressing DN and DR is associated with the duration of diabetes. These complex disorders are strongly influenced by both genetics and environmental factors. Several candidate genes have been reported to be associated with DN and DR in different populations. Aim: To determine the co-existence of DN and DR in relation to gene polymorphisms of Angiotensin-Converting Enzyme (ACE), Angiotensinogen (AGT), Receptor for Advanced Glycation End-products (RAGE), Aldose reductase (ALR2), and Vascular Endothelial Growth Factor (VEGF). Materials and Methods: The present DN and DR cross-sectional study was conducted at the Department of Endocrinology, University College of Medical Sciences, University of Delhi and GTB, New Delhi, India, and the Discipline of Biochemistry, Indira Gandhi National Open University, New Delhi, India. The study was conducted from October 2019 to August 2022. All the participants under uniform diabetes management were divided into two groups (100 in each group): Group 1 included Type-II diabetic patients with DN and DR, and Group 2 comprised Type-II diabetic patients with DN only. Polymorphisms in all genes were determined using Polymerase Chain Reaction (PCR), followed by digestion with restriction enzymes and visualisation through an ultraviolet transilluminator. The analysis of biochemical parameters and association of gene polymorphisms was performed using Statistical Package for Social Sciences (SPSS) version 26.0 software. Results: There were 57 males and 43 females in the DN+DR group, and 51 males and 49 females in the DN-DR group. The mean age of study subjects in the DN+DR group was 52.60±9.08 years, compared to the DN-DR group (47.33±10.68 years). The DN+DR group had a significantly higher mean duration of diabetes (11.78±6.86 vs. 5.13±4.78, p≤0.001) and a significantly lower mean waist circumference (91.30±13.99 vs. 95.11±9.95 cm, p≤0.02). The DN+DR group also had significantly higher urea (34.34±16.32 vs. 26.43±12.34 cm, p≤0.001), creatinine (1.34±0.90 vs. 0.89±0.25 cm, p≤0.03) and significantly lower estimated Glomerular Filtration Rate (eGFR) levels compared to the DN-DR group. The distribution of genotypes of ALR2 (p≤0.04) and VEGF genes (p≤0.001) showed a significant difference between both DN+DR and DN-DR groups. The frequency of the D allele of the VEGF gene (p≤0.02) (OR=1.94, 95% Confidence Interval (CI)=1.10-3.40) was higher in the DN+DR group. The DN+DR group also had a significantly lower frequency of the CT+TT dominant model of the ALR2 gene (p≤0.04) as well as an increased frequency of the ID+DD dominant model of the VEGF gene (p≤0.002). No significant differences were found in genotypic as well as allelic frequencies of ACE, AGT, and RAGE gene polymorphisms between the two groups. Conclusion: The D allele of the VEGF (I/D) gene polymorphism is significantly associated with DR in patients with DN. It can be concluded that the VEGF gene plays an important role in the development of retinopathy in DN patients.

Gene polymorphisms of VEGF and KDR are associated with initial fast peritoneal solute transfer rate in peritoneal dialysis

BackgroundPeritoneal dialysis (PD) is an effective and successful renal replacement therapy. The baseline peritoneal solute transfer rate (PSTR) is related to local membrane inflammation and may be partially genetically determined. Herein, we focused on vascular endothelial growth factor (VEGF) and its receptor, kinase insert domain containing receptor (KDR).MethodsThis study recruited 200 PD patients from Renji Hospital in Shanghai, China. We analysed the association between the polymorphisms of VEGF and KDR and the 4-hour dialysate-to-plasma ratio for creatinine (4 h D/P Cr), which was measured between one and three months after initiating PD.ResultsThe CC genotype in VEGF rs3025039 and the AA genotype in KDR rs2071559 were both positively associated with a fast baseline PSTR (VEGF rs3025039 CC vs. TT + TC: 0.65 ± 0.12 vs. 0.61 ± 0.11; P = 0.029; KDR rs2071559 AA vs. GA + GG: 0.65 ± 0.12 vs. 0.62 ± 0.12; P = 0.039).ConclusionBaseline PSTR was partly determined by VEGF and KDR gene polymorphisms.

Analysis of vascular endothelial growth factor (VEGF) insertion/deletion gene polymorphism and environmental risk factors in sample of Algerian population with neovascular age-related macular degeneration (nAMD)

Increasing evidence shows that genetic and environmental factors can influence neovascular age-related macular degeneration (nAMD) risk. The aim of this study was first to analyse the association of insertion/deletion polymorphism in VEGF gene and environmental factors with the risk of nAMD, and then to investigate whether these factors have an impact on the age of onset of nAMD in a sample of the Algerian population. Seventy two patients with nAMD and one hundred twenty-four controls were recruited; standardized questionnaire was used to collect information regarding underlying systemic diseases and important environmental factors. Genotyping of VEGF (I/D) SNP was conducted using PCR-based assay approach, and statistical analyses were conducted using IBM SPSS statistics 21. A significant association was reported of age (p < 0.05), smoking (p = 0.02), alcohol (p < 0.01), hypertension (p = 0.04), hyperlipidaemia (p = 0.008) and thyroid disease (p = 0.03) with nAMD. Also, Thyroid disease may have a role in accelerating the development of nAMD in an earlier age in our sample (p < 0.001). No association was found between the VEGF – 2549 I/D genotype and the presence of nAMD (p = 0.27), neither with the age of onset of nAMD (p = 0.21). Our results suggest that age, smoking, alcohol, hypertension, hyperlipidaemia and thyroid diseases are possible risk factors that could increase the risk of nAMD in a sample of Algerian population. In addition, VEGF – 2549 I/D might not be associated with the risk of nAMD development. Finally, thyroid disease may accelerate the development of nAMD in an earlier age.

Interaction Between Vascular Endothelial Growth Factor Gene Polymorphism and Smoking on Gastric Cancer Risk in Chinese Han Population.

Aim: In this study, we aimed to evaluate the associations of vascular endothelial growth factor (VEGF) gene single nucleotide polymorphisms (SNPs) and its interaction with current smoking with gastric cancer (GC) risk in the Chinese Han population. Methods: We used logistic regression model to test the association between VEGF gene polymorphism and the risk of GC. The association strength was evaluated by odds ratio (OR) and 95% confidence interval (CI) calculated using logistic regression. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the effect of the interaction between VEGF gene and current smoking on GC risk. Results: Logistic regression analysis showed that the risk of GC was significantly higher in rs10434 -G allele carriers than that in AA genotype carriers (AG + GG and AA), and the adjusted OR (95% CI) = 1.64 (1.24–2.08). In addition, we found a significantly higher GC risk in subjects with rs833061-T allele than those with CC allele (CT + TT and CC), adjusted or (95% CI) = 1.43 (1.10–1.87). We also found a statistically significant two- locus model (p = 0.018), including rs10434 and current smoking, indicating a significant interaction between rs10434 and current smoking on the risk of GC. Hierarchical analysis found that current smokers with AG or GG genotype have the highest GC risk, compared to never- smokers with AA genotype, OR (95% CI) = 2.43 (1.64–3.28). Conclusion: We found that rs10434 -G and rs833061-T alleles, gene- environment interaction between rs10434, and current smoking were all related to increased GC risk.

VEGF Gene Polymorphism Among Diabetes Mellitus and Diabetic Retinopathy

Vascular endothelial growth factor (VEGF) is a major angiogenic factor and a prime regulator of endothelial cell proliferation. VEGF gene is located on chromosome 6 (6p21.3). Objectives: To determine whether deletion at -2549 position of promoter region of the VEGF gene exert influence on the development of diabetic retinopathy. Methods: Diseased and control subjects were selected for blood sampling. The blood samples (n=50) was taken from diabetic retinopathy patients and blood samples(n=50) was taken from type 2 diabetes mellitus patients as control group. After DNA extraction Polymerase Chain Reaction was performed to amplify the VEGF gene and sequencing was commercially done for molecular analysis of VEGF gene. Results: The molecular analysis confirmed that deletion at -2549 position of the promoter region of VEGF significantly greater in DR group. 2-11 % deletion was examined at -2549 position of promoter region of VEGF. The DD genotype was responsible for the development of DR. Conclusions: This study indicates that DD gene mutation and D allele is an autonomous hazard aspect for the advancement and progression of retinopathy in people with type 2 diabetes, additionally different issues for example diabetic age and family ancestry of diabetes assumes key function in the advancement of retinopathy in diabetic patients.

Association of VEGF Gene Polymorphism (rs699947) with Glaucoma and In-Silico Study of Antiglaucoma Bioactive Compounds.

Vascular endothelial growth factor (VEGF) is a useful expert in various maturation and other problems such as glaucoma. VEGF gene is located on the short arm of chromosome 6. It has 8 exons and 6 introns. This investigation was planned to check out the relationship of VEGF polymorphism with glaucoma patients and to cause in silico limitation of carbonic anhydrase to diminish the intraocular strain of watery humor to fix glaucoma. In this examination, a large portion of the glaucoma patients (n = 70) were males (66%) when contrasted with females (34%) as the p-value was 0.025 which showed critical outcomes and subsequently demonstrated that the sickness was more predominant in males. Glaucoma for the most part influences people between the ages of 50-60years followed by the age bunch between 30 and 40years. Around 36 (51.4%) were experiencing watering in the eyes, 28 (40%) had photophobia, 9 (12.8%) had a hazy cornea, 6 (8.6%) had expanded eye globe, and 15 patients (21.3%) had rosy eyes. Factual tests showed that VEGF quality SNP rs699947 had no huge relationship with glaucoma (POAG). In this study, various carbonic anhydrase inhibitor phytochemicals and synthetic chemicals were screened in silico which may be used as antiglaucoma drugs.

152P Prognostic impact of serum vascular endothelial growth factor and VEGF gene polymorphism (rs2010963) in breast cancer patients

Vascular Endothelial Growth Factor (VEGF) mediates breast carcinogenesis, several studies shown that VEGF is associated with increased breast cancer risk however its prognostic significance and expression in different molecular subtypes remain unclear. The current study aimed to evaluate the diagnostic and prognostic role of serum VEGF and VEGF rs2010963 polymorphism in Egyptian women with breast cancer.

Relationship between Gene Polymorphism of Vascular Endothelial Growth Factor (VEGF) rs699947 with VEGF and Matrix Metalloproteinase-14 Protein Levels in Patient with Diabetic Foot Ulcer

BACKGROUND: Vascular endothelial growth factor (VEGF) protein levels in diabetes mellitus (DM) patients with ulcerative foot will tend to decrease. Matrix metalloproteinases (MMPs) and their inhibitors have also been identified in regulating capillary tubes formation (morphogenesis) with the collagen matrix, associated with the formation and regression of granulation tissue during the wound healing process. AIM: This study was aimed to determine the relationship between gene polymorphism VEGF rs699947 with VEGF and MMP-14 protein levels in cases of diabetic foot ulcers (DFUs). METHODS: This study was an observational research with cross-sectional comparative study design. The population in this study were type-2 DM patients who met the inclusion criteria. According to the Meggitt-Wagner classification, the study sample was divided into two groups: Type 2 DM group without DFU and type 2 DM group with DFU Grades 1–3. RESULTS: In this study, there were differences in the protein levels of MMP-14 (p = 0.039) VEGF (p = 0.002) between type-2 DM patients with and without FDU. However, there was no difference in the VEGF gene polymorphism rs6999947 between type-2 DM patients with and without FDU (p = 0.099). In addition, the results showed that type-2 DM patients with MMP-14 protein levels ≤ 3.864 had a 3.6 times greater risk of suffer FDU compared to type-2 DM patients with MMP-14 protein levels &gt; 3.864 but not significant (PR = 3.600 (IK 5 % 1.142–11.346); p = 0.052). Meanwhile, type 2 DM patients with VEGF protein levels ≤567.42 were significantly more at risk of 9048 times to suffer FDU compared to type 2 DM patients with VEGF protein levels &gt; 567.42 (PR = 9.048 (CI 5% 2.571–31.842); p = 0.001). CONCLUSION: In type 2 DM patients with FDU, there were lower levels of MMP-14 and VEGF compared to patients without FDU. There is a significant relationship between VEGF protein levels and the incidence of FDU in type 2 DM patients, but there is no relationship between MMP-14 and the gene polymorphism VEGF rs6999947 with the incidence of FDU in type 2 DM patients.

Association between VEGF Gene Polymorphism -634G&gt;C and Risk of Colorectal Cancer

BACKGROUND: Genetic and environmental factors play an important role in the pathogenesis of colorectal cancer. Angiogenesis is a central process in carcinogenesis and is affected by vascular endothelial growth factor (VEGF). Several genetic variations, such as polymorphism, may alter VEGF expression and influence the risk of colorectal cancer. AIM: The objective of this study was to determine the association between VEGF gene polymorphism -634G&gt;C and risk of colorectal cancer. METHODS: A cross-sectional study was conducted at Haji Adam Malik general hospital and its sister hospitals. Subjects were obtained by consecutive sampling. Inclusion criteria for case and control groups were patients with colorectal cancer and healthy subject, respectively, aged 18 years or older and willing to participate in the study. Exclusion criteria were patients with systemic comorbidities or malignancies in other organs. Each subject undergoes an interview, colonoscopy, biopsy, serum VEGF level measurement, and VEGF polymorphism -634G&gt;C evaluation. RESULTS: Eighty subjects were enrolled and distributed into case and control groups. Males were dominant in both groups, with a mean age of older than 55 years. Most lesions were in the rectum and 45% of subjects had moderately differentiated cancer. The median serum VEGF level in the case group was higher than the control group (2,175.1 pg/mL vs. 253 pg/mL; p &lt; 0.001). VEGF gene polymorphism -634G &gt; C was associated with the risk of colorectal cancer (p = 0.048). GG and GC genotypes had 1.89 times higher risk of colorectal cancer compared to the CC genotype. GG genotype and G allele had the highest serum VEGF levels. CONCLUSION: There is an association between VEGF gene polymorphism -634G&gt;C and risk of colorectal cancer in this study.

Associations between AGT, MTHFR, and VEGF gene polymorphisms and preeclampsia in the Chinese population.

Preeclampsia (PE) is a pregnancy-specific multisystemic syndrome. This study aimed to investigate the associations between angiotensinogen (AGT), methylenetetrahydrofolate reductase (MTHFR), vascular endothelial growth factor (VEGF) polymorphisms, and PE in the Han Chinese population. We genotyped 26 single-nucleotide polymorphisms (SNP) in three genes by using QuantStudio™ 12K Flex Real-Time PCR technology in 168 patients with PE and 204 healthy pregnant control subjects. The associations of tested polymorphisms with PE were analyzed at allele, genotype, and haplotype levels. A common coding variant in MTHFR, rs2274976, was significantly associated with increased risk of PE in both allelic and genotype models (P<0.05). The heterozygous genotypes of rs699 (G/A vs G/G) in AGT gene and rs3025035 (C/T vs C/C) in VEGF gene showed weak associations with increased PE risk, whereas the mutant homozygous genotype of rs3024987 (TT vs C/C) and the heterozygous genotype of rs3025039 (C/T vs C/C) in VEGF gene displayed weak associations with decreased PE risk (P<0.05). However, these weak associations lost significance after multiple testing correction. The results indicated that rs2274976 in MTHFR gene may contribute to the increased risk of PE in pregnant women. AGT and VEGF gene polymorphisms may not play a significant role in PE development.

POS-804 Donor vascular endothelial growth factor gene polymorphism association with acute allograft rejection in live related renal transplant recipient patients

Renal allograft rejection risk associated with donor’s vascular endothelial growth factor (VEGF) gene polymorphism remain unelucidated till now. Although, studies have shown, an association of recipient’s VEGF polymorphism with the end-stage renal disease and early acute rejection. VEGF has pleiotropic function, which regulates vasculogenesis, endothelial cell survival signaling. Endothelial cell regulates tonicity, the permeability of blood vessels and egression of allo-stimulated inflammatory cell in intragraft compartments, thus regulate the events of rejection. In the current study, we aimed to investigate the distribution of VEGF -634C>G, -1154 G>A, -1190G>A, -1455T>C, -1499 C>T, -2578 C>A, -2549 18bp Insertion/Deletion, +405 C>G and +936 C>T SNPs among donors and recipients and to evaluate the VEGF mRNA and protein expression in intragraft tissue and in plasma. We analyzed VEGF gene polymorphism in 160 Kidney donor and 320 Kidney allograft recipients (n=160, rejecters and n=160, non-rejecters patients). One hours prior to patient admission in kidney transplant unit, a 5 ml of blood was collected in K2EDTA vials for plasma, DNA and RNA isolation from donor and recipients. After centrifugation at 1500RPM for 5 minutes, plasma supernatants were separated and 1ml cell pellet was used for DNA isolation and 1 ml pellet was dissolved in Trizole solution for RNA isolation. A core of allograft biopsy specimen was collected from 50 patients for allograft recipient for VEGF gene and protein expression in intragraft tissue by the RT-PCR and Immunohistochemistry techniques respectively and soluble plasma VEGF level was analyzed by the ELISA. Genotyping of VEGF SNPs were done through PCR- RFLP technique. Difference between donor and recipient group was calculated by the Fisher exact test. P value <0.05 was considered statistically significant. The odd ratio was calculated to measure the difference in association between genotypes. On comparison between donors and recipients genotypes of VEGF +936 C>T [CT (OR=7.16; 95% CI=4.33- 11.84; P=0.00) and TT (OR=49.30; 95% CI=11.84-205.29; P=0.00)], -1154 G>A [AG (OR=2.22; 95% CI=1.40-3.50; P=0.00)], -1190G>A [GG (OR=2.21; 95% CI=1.22-4.01; P=0.00)], -634C>G [GG (OR=2.34; 95% CI=1.34-4.10; P=0.00)], -2549 18bp Insertion/Deletion [ID (OR=1.58; 95% CI=1.01- 2.46; P=0.04) were significantly associated with risk of rejection. Genotypic frequencies of +936 C>T [TT (OR=2.43; 95% CI=1.33-4.44; P=0.004)], -1154 G>A [GG (OR=1.94; 95% CI=1.03-3.67; P=0.04)], -1190G>A [GA (OR=1.83; 95% CI=1.07-3.13; P=0.02)], -2549 18bp Insertion/Deletion [ID (OR=2.35; 95% CI=1.38- 3.99; P=0.002) and -1455T>C [TT (OR=3.13; 95% CI=1.07-9.10; P=0.03)] shown risk of allograft rejection whereas mutant genotypes of -2578 C>A [ CA (OR=0.45; 95% CI=0.26-0.79; P=0.005) and CC (OR=0.23; 95% CI=0.11-0.46; P=0.000)] and +405 C>G [GG (OR=0.43; 95% CI=0.20-0.91; P=0.02)] have shown protective association with rejection. The intragraft VEGF mRNA and protein expression and plasma soluble VEGF level was significantly higher in allograft recipients compared to healthy donor, which was further higher in rejecters compared to non-rejecters. Mutant genotypes of VEGF +936 C>T, -1190G>A, -2549 18bp Insertion/Deletion and -1455T>C SNPs was associated with increased risk for allograft rejection

Influence of vascular endothelial growth factor on neutrophil activation in asthmatics.

IntroductionAsthma is a complex syndrome associated with heterogeneity in the type of inflammation that modulates airway hyperresponsiveness and remodelling. Airway inflammation with neutrophils, cytokines like vascular endothelial growth factor (VEGF) and various gene polymorphisms might be relevant for asthma pathogenesis.AimTo investigate the expression of CD69 and CD11b markers on peripheral neutrophils after VEGF in vitro stimulation in asthmatics. Furthermore, the possible influence of a genetic factor (del/ins genotype at -2549 -2567 position in the VEGF-promoter gene) was taken into account.Material and methods122 subjects (82 asthmatics and 40 controls) participated in our study. CD69 and CD11b presence on peripheral blood neutrophils was detected using the flow cytometric method without exogenous stimulation (negative control), after N-formyl-methionine-leucyl-phenylalanine stimulation (fMLP – positive control) and after VEGF stimulation. Genotyping for the VEGF-promoter region was performed by polymerase chain reaction (PCR).ResultsPeripheral neutrophil stimulation with VEGF enhances the activity of these cells and induces CD69 and CD11b expression in a dose-dependent manner compared with unstimulated neutrophils (p > 0.05). CD69 and CD11b markers were slightly presented (p = 0.05 and p = 0.07, respectively) on neutrophils stimulated with fMLP in asthmatics with the ins genotype variant in the VEGF-promoter region.ConclusionsOur results demonstrate that VEGF might insignificantly activate neutrophils in asthmatics. In addition, the modulated expression of CD69 and CD11b on peripheral neutrophils is not related to potential contribution of the VEGF gene polymorphism.

Determination of serum vascular endothelial growth factor (VEGF) and VEGF receptor levels with VEGF gene polymorphisms in patients with Behçet’s uveitis

Behçet's disease (BD) is a chronic inflammatory vasculitis affecting multiple organs. Uveitis is frequently seen in patients with BD, especially in Turkish population. To investigate vascular endothelial growth factor (VEGF) gene polymorphisms along with the levels of VEGF and VEGF receptors in patients with Behçet's uveitis (BU). Fifty-five BD-associated uveitis patients and 30 ageand sex-matched controls were included in this case-control study. The genotypes of the single nucleotide poymorphisms (SNPs): rs2010963 (+405G), rs3025039 (+936T) and rs699947 (-2598A) of the VEGF-A gene were determined using real-time polymerase chain reaction (RT-PCR) and serum levels of VEGF and VEGF receptors were measured using enzyme-linked immunosorbent assay (ELISA). No associations of the VEGF gene polymorphisms were observed in BD uveitis patients, but arthritis was present in 53.3% of patients not possessing CT genotype in C3025039→T polymorphism (p = 0.024). Although there were no statistically significant differences in serum VEGF-A, VEGF-C and soluble vascular endothelial growth factor receptor-3 (sVEGFR-3) levels (p < 0.05), serum vascular endothelial growth factor receptor-1 (VEGFR-1) and sVEGFR-3 levels were significantly higher in the BD group (p < 0.001 and p = 0.001, respectively). In addition, VEGF-C/soluble vascular endothelial growth factor receptor-2 (sVEGFR-2) ratio was significantly higher (p < 0.001), while VEGF-A/VEGFR-1 and VEGF-C/sVEGFR-3 ratios were significantly lower (p < 0.001 and p = 0.033, respectively) in BD patients compared to controls. Also, VEGF-C/sVEGFR-3 (p = 0.024, r = 0.37) and VEGF-C/sVEGFR-2 (p = 0.020, r = 0.38) ratios were positively correlated with disease duration. The significant changes in sVEGFR-3 levels and VEGF-C/sVEGFR-3 ratio has shown that lymphangiogenesis processes might take place in the pathogenesis of BD uveitis, and these parameters can be important indicators of evaluation of BD patients with uveitis together with disease duration.

Effect of vascular endothelial growth factor gene polymorphisms on disease activity in rheumatoid arthritis

BackgroundThe full etiology of RA remains unclear; in addition to the contributions of infectious, hormonal, and environmental factors, several lines of evidence have suggested that the disease has a genetic basis. The VEGF gene is also an independent risk factor for RA severity and correlates with multiple disease parameters, such as disease activity, joint damage, and functional disability. This case-control study aimed to investigate the impact of a common genetic polymorphism in the vascular endothelial growth factor (VEGF) gene on disease activity and synovial lesions in patients with rheumatoid arthritis (RA).ResultsT allele was present in the RA group more frequently (22.5% vs. 10% respectively in controls). The C allele was less frequent in the RA group (77.7% vs. 90% respectively in controls) (P = 0.002). Homozygous genotype (CC) was found in 61.2% of patients and 82.5% of controls, homozygous genotype (TT) in 6.3% of patients, and 2.5% of controls while heterozygous (CT) genotype in 32.5% of patients and 15% of controls (P = 0.011). Grade 1 PDUS was found in 30.6% of CC and 11.5% of CT and not found in TT genotypes. The grade 2 was found in 69.4%, 65.4%, and only 20% of CC, CT, and TT genotypes, respectively. The grade 3 was found in 80% of TT, 23.1% of CT, and none of CC genotypes (P < 0.001).ConclusionAn association between VEGF gene SNP rs3025039 and increased risk for RA among a sample of Egyptian population was noticed. VEGF gene polymorphism appears to be a potential diagnostic activity indicator and a promising therapeutic target for RA patients.

Association between single nucleotide polymorphisms of VEGF gene and pelvic lymph node metastasis in patients with early-stage cervical cancer

Cervical cancer patients in early-stage cervical cancer (ECC) were divided into pelvic lymph node (PLN) metastasis and non-PLN metastasis group. Single nucleotide polymorphism (SNP) genotyping for the VEGF gene was conducted and plasma VEGF levels were measured. Multivariate analysis was performed to assess the correlation between SNPs of the VEGF gene and PLN metastasis. We found that SNP of the VEGF rs2010963 was independently associated with PLN metastasis. GG and CG genotype had increased susceptibility to PLN metastasis compared with CC genotype, and moreover, OR was higher in GG genotype than in CG genotype. Plasma VEGF levels were lowest in CC genotype, intermediate in GC genotype and highest in GG genotype. In summary, the SNP of the VEGF rs2010963 affected susceptibility to PLN metastasis in patients with ECC, and GG and CG genotype had increased susceptibility compared with CC genotype. The potential mechanism was associated with elevated plasma VEGF levels. Impact Statement What is already known on this subject? The positive expression of vascular endothelial growth factor (VEGF) is correlated with higher risk of lymph node metastasis among cervical cancer patients, and VEGF levels of patients with pelvic lymph node (PLN) metastasis are significantly higher than those without PLN metastasis. Additionally, single nucleotide polymorphisms (SNPs) of the VEGF gene have been indicated to be correlated with individual susceptibility to tumours and expression and protein production of VEGF. What do the results of this study add? The SNP of the VEGF rs2010963 was independently associated with PLN metastasis in patients with early-stage cervical cancer (ECC). The GG and CG genotype of the VEGF rs2010963 had increased susceptibility to PLN metastasis compared with CC genotype. Plasma VEGF levels were lowest in the CC genotype, intermediate in the GC genotype and highest in the GG genotype. What are the implications of these findings for clinical practice and/or further research? The SNP of the VEGF rs2010963 affected susceptibility to PLN metastasis in patients with ECC, and the potential mechanism was associated with elevated plasma VEGF levels.

Association of vascular endothelial growth factor gene polymorphism with psoriasis

Background Psoriasis is an immune-mediated complex cutaneous disorder. In its pathologic process, there is abnormal keratinocyte differentiation and proliferation, as well as inflammation, besides abnormal vascular expansion. Vascular endothelial growth factor (VEGF) acts as a potent mediator of inflammation and angiogenesis in psoriasis. Objective This work aimed to study the role of VEGF gene polymorphism (rs2010963) in psoriasis vulgaris. Patients and methods This case–control study covered 45 patients with psoriasis vulgaris and 45 age-matched and sex-matched healthy participants as a control group, and had been checked to discover C-G transition polymorphism at position +405 of the VEGF gene by a real-time PCR. Results There was a significant difference between cases and controls concerning the distribution of VEGF gene polymorphism (P = 0.046), and also, there was a statistically significant difference between cases and controls concerning VEGF alleles (P = 0.036). Conclusion There was a significant association between the genotypes of the VEGF gene polymorphism and psoriasis vulgaris, suggesting that the VEGF gene polymorphism may have a possible active role in the etiopathogenesis of psoriasis vulgaris.

Low level of plasma VEGF-A and C allele of -2578*C/A polymorphism in the VEGF-A gene are risk factors of diabetic foot ulcer in Javanese ethnic

Diabetes mellitus (DM) is caused by abnormal insulin secretion, impaired insulin action, or both. Approximately 12-25% of type 2 diabetes mellitus (T2DM) patients will develop diabetic foot ulcers (DFU). Vascular endothelial growth factor (VEGF) is a group of platelet-derived growth factors (PDGF) which have a potential role in angiogenesis. Low levels of VEGF-A can cause insufficient angiogenesis leading to wound healing inhibition. The 2578*C/A polymorphism of VEGF-A gene has been reported as a candidate marker for the DFU development. However, the variant role in the development of DFU in Javanese ethnic needs to be clarified. This study was conducted to compare VEGF-A levels and the -2578*C/A polymorphism of the VEGF gene among diabetic patients with and without DFU in Javanese ethnic. In this case-control study, the T2DM individuals with DFU as case group (n=19) and without DFU as control group (n=41) were recruited. The VEGF-A levelswere determined by ELISA. The ARMS-PCR technique was applied to investigate the presence of -2578*C/A polymorphism of the VEGF gene. Data were analyzed with independent t, Mann-Whitney, Chi-square, and Kruskal-Wallis tests with significance level of p&lt;0.05. The median of plasma VEGF-A level was significantly different between case and control groups (p=0.001). The genotype frequency of -2578*C/A polymorphism of VEGF gene was no difference between case and control groups. However, individuals with C allele have a higher risk factor to develop DFU than A allele (CC+CA vs AA;p=0.042; OR=2.5). The plasma VEGF-A levels were lower in T2DM subjects with DFU than those without DFU. In conclusion,individuals with C allele of -2578*C/A polymorphism of VEGF gene are more susceptible to have DFU than individuals with A allele in Javanese ethnic with T2DM.

Effects of VEGF Gene Polymorphisms on BEV Responsiveness in a Sample of Iraqi Colorectal Cancers Using HRM - PCR

Background: Vascular endothelial growth factor (VEGF) have a vital role in the molecular genetic eventsof angiogenesis and vasculogenesis, so it is involved in the development of cancer. Single nucleotidepolymorphisms (SNP) in VEGF gene has been announced as a risk factor in colorectal cancer. Bevacizumab(BEV) is an angiogenesis inhibitor that curb the binding of VEGF to its receptors obstructing the angiogenesisprocess. Objective: The ideal goal of ongoing study lies in revealing the effect of rs699947 (-2578 C/A (andrs833061 (-460C/T( polymorphisms in the promoter of VEGF gene on the development of colorectal cancerand on the BEV responsiveness in a sample of Iraqi patients using High Resolution Melting Analysis (HRM)analysis. Methodology: Venous blood samples were collected from 25 colorectal cancer patients withresponse to BEV treatment and 25 with BEV resistant and 25 apparently healthy individuals as controlgroup who matched with patients in age and gender. Results: AA and CA polymorphisms A allele ofrs699947 (-2578 C/A) and TT and CT polymorphisms and T allele of rs833061 (-460C/T( were representa risk factor on the occurrence of the colorectal cancer. It has been found that CC and CA polymorphismof the VEGF - 2578 C/A and CT genotype of the VEGF -460 C/T polymorphism might be a predictivefactors of responsiveness to BEV chemotherapy in CRC patients. Conclusion: These outcomes confirm theessential role that VEGF polymorphisms play in the occurrence of CRC and the correlation between SNPs inVEGF promoter region and the BEV responsiveness. With this, further research and investigation of VEGFpolymorphisms could allow for its use in identifying risk factors for the development of CRC and increasingits predictive value for anti-VEGF cancer therapies.