Vascular Endothelial Growth Factor Rs2010963 Research Articles

Effect of <i>VEGF</i> gene polymorphism on the survival of a patient with non-small cell lung cancer

Currently, much attention is paid to studying the vascular endothelial growth factor (VEGF) that stimulates angiogenesis, as a potential target for antiangiogenic therapy. The purpose of this work was to study the effect of polymorphic variants rs2010963 (G-634C), rs699947 (A-2578C), and rs3025039 (C+936T) of the VEGF gene, encoding a vascular endothelial growth factor, on the overall (OS) and adjusted survival (AS) of patients with non-small cell lung cancer (NSCLC) at stages I–III. The effect of VEGF rs699947 polymorphic variants on the extent of tumor spread was shown. A connection between AS and polymorphic variants rs2010963 (G-634C) and rs699947 (A-2578C) was established. The one-year adjusted survival (AS) in the -634G/C genotype carriers was 81.9 ± 3.9 %; in the -634G/G genotype carriers – 92.8 ± 2.5 %; and p = 0.016 was the significance level. Two-year AS was as follows: in the carriers of the -634G/C genotype was 70.4 ± 4.6 %; in the carriers of the -634G/G genotype – 84.3 ± 3.5 %; and p = 0.015. Three-year AS: in the carriers of the -634G/ genotype C was 63.0 ± 4.9 %; in the carriers of the -634G/G genotype – 76.7 ± 4.1 %; and p = 0.029. One-year and two-year AS in the carriers of the -2578A/A genotype was significantly higher than in the carriers of the -2578C/C genotype (p = 0.015 and p = 0.042 respectively). The identified influence of the polymorphic variants rs2010963 and rs699947 on the survival of NSCLC patients during the first three years after the established diagnosis shows a need to use knowledge about the genetic characteristics of a tumor during therapy.

The potential impact of vascular endothelial growth factor rs699947 polymorphisms on breast tumors susceptibility in a sample of iraqi females

The potential impact of vascular endothelial growth factor rs699947 polymorphisms on breast tumors susceptibility in a sample of iraqi females

Vascular Endothelial Growth Factor Polymorphism rs699947 Is Associated with Neurostructural Phenotypes in Youth with Bipolar Disorder.

Background: Vascular endothelial growth factor (VEGF) may be relevant to bipolar disorder (BD) and brain structure. We evaluated VEGF rs699947 single-nucleotide polymorphism in relation to structural neuroimaging phenotypes in youth BD. Methods: We collected 3 T anatomical magnetic resonance images from 154 youth (79 BD and 75 healthy control [HC]) genotyped for VEGF rs699947. The participants were age (BD = 17.28 ± 1.40 and HC = 17.01 ± 1.83, t = -1.02, p = 0.31) and sex (BD = 63.3% females and HC = 52.0% females, χ2 = 2.01, p = 0.16) matched. Cortical thickness, surface area (SA), and volume were examined by region-of-interest (ROI) and vertex-wise analyses using general linear models (GLMs). ROI investigations selected for the prefrontal cortex (PFC), amygdala, and hippocampus. Vertex-wise analyses controlled for age, sex, and intracranial volume. Results: ROI results found lower PFC SA (p = 0.003, ηp2 = 0.06) and volume (p = 0.04, ηp2 = 0.03) in BD and a main effect of rs699947 on hippocampal volume (p = 0.03, ηp2 = 0.05). The latter two findings did not survive multiple comparisons. Vertex-wise analyses found rs699947 main effects on left postcentral gyrus volume (p < 0.001), right rostral anterior cingulate SA (p = 0.004), and right superior temporal gyrus thickness (p = 0.004). There were significant diagnosis-by-genotype interactions in the left superior temporal, left caudal middle frontal, left superior frontal, right fusiform, and right lingual gyri, and the left insular cortex. Posthoc analyses revealed the AA allele was associated with larger brain structures among HC, but smaller brain structures in BD for most clusters. Conclusions: Overall, we found preliminary evidence of divergent associations between BD and HC youth in terms of neurostructural correlates of VEGF rs699947 encompassing highly relevant frontotemporal regions.

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.

Investigation of the effect of vascular endothelial growth factor gene 936 C/T polymorphism in familial Mediterranean fever patients

Objectives: This study aims to investigate the effect of vascular endothelial growth factor (VEGF) gene 936C/T polymorphism (rs3025039) on the appearance of phenotypic characteristics of familial Mediterranean fever (FMF) patients that differ with respect to MEditerranean FeVer (MEFV) gene mutations. Here, we investigated a single functional polymorphism in the VEGF gene. Methods: The study group consisted of 223 FMF patients with definite diagnosis according to Tel-Hashomer criteria who carried MEFV gene mutations, while 208 FMF patients with definite diagnosis of FMF but without any mutations, making up the control group, were included in the study. The VEGF gene 936C/T polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Results: Genotype and allele frequencies of the VEGF rs3025039 polymorphism between the two groups were significantly different (p = 0.03 and p = 0.011, respectively). The TT genotype was found to be more frequent in the study group than in controls (4.9% vs. 3.3%, respectively). Conclusions: Our results seem to indicate that the VEGF 936C/T polymorphism affects the appearance of the phenotypic characteristics of FMF. It is possible that other variants of this gene may also have similar effects.

Association of polymorphisms of VEGF and VEGFR1 pathways related genes and risk of pre-eclampsia

To assess the association of single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 1 (VEGFR1) pathways-related genes and the risk of pre-eclampsia. In total 178 pregnant women with pre-eclampsia (case group) and 100 healthy pregnant women (control group) during the third trimester were enrolled. The SNPs of VEGF rs3025039, rs2010963 and VEGFR1 rs3812867, rs55875014 and rs722503 loci were determined by PCR-restriction fragment length polymorphism (PCR-RFLP) assay. The levels of serum VEGF and sVEGFR1 were also determined. And their association with pre-eclampsia was analyzed. The systolic blood pressure, diastolic blood pressure and sVEGFR1 of the case group were significantly higher than those of the control group, while the VEGF level was significantly lower than that in the control group (P<0.05). Allelic frequencies of the VEGF (rs3025039, rs2010963) and VEGFR1 (rs3812867, rs55875014, rs722503) have fit the Hardy-Weinberg equilibrium (P>0.05). The frequency of T allele of VEGF at rs3025039 locus in the case group was higher than that in the control group (P<0.05). There were significant differences in VEGF at rs3025039 locus under dominant and co-dominant models in case group (P<0.05). Compared with those with CC, the risk was higher in patients with CT or TT genotypes (P<0.05). The systolic and diastolic blood pressure and sVEGFR1 in pre-eclampsia pregnant women with CT or TT genotypes were significantly higher than those with the CC genotype, while their VEGF level was significantly lower (P<0.05). No significant difference was found in allelic frequencies of other four loci between the two groups (P>0.05). Polymorphisms of rs3025039 locus of VEGF gene is associated with the occurrence of pre-eclampsia. The variant at this locus may affect the activity of VEGF and influence the development of pre-eclampsia.

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.

VEGF and eNOS genes polymorphism features in patients with diabetes mellitus with and without initial non-proliferative diabetic retinopathy

The endothelial NO synthase (eNOS) and vascular endothelial growth factor (VEGF) imbalance and the polymorphism of these genes may be the predisposition for diabetic retinopathy (DR) development and progression.The aim: to analyze VEGF (rs699947 and rs3025039) and eNOS (rs2070744) genes polymorphism and their combinations in patients with type 2 diabetes mellitus (DM2) with and without initial non-proliferative DR.Materials and methods. The study included 200 patients with type 2 diabetes (155 women and 45 men, age – 43–70 years): 111 people without and 89 people with DR. The polymorphism of the regulatory regions of VEGF (rs699947 and rs3025039) and eNOS (rs2070744) genes was studied using restriction fragment length polymorphism analysis and TaqMan Real-Time PCR by. Statistical processing was carried out using the software packages Statistica 10.0, SPSS Statistics 23 and the package of original programs for volumetric processing of bioinformation.Results. The VEGF-2578 heterozygosity and two complex genotypes – VEGF-2578CA:VEGF+936CC and NOS3-786CT:VEGF-2578CA:VEGF+936CC – signifi cantly decreased in patients with DR. The predisposition to early DR development to minor genotype of eNOS gene in the NOS3-786CC:VEGF+936CT complex and signifi cantly decreased the homozygous wild-type eNOS genotype in DM2 patients with ophthalmopathology were shown. NOS3-86TT:VEGF2578AA genotype signifi cantly decreased in group with retinopathy developing and the glycated hemoglobin high level.Conclusion. Along with the clinical risk factors for the development of DR in DM2, the genetic polymorphism of the regulatory regions of the genes analyzed by us has a signifi cant weight. When analyzing potential genetic markers, it is important to consider possible joint epistatic/hypostatic effects. The complex analysis of polymorphic gene can help early prognosis of the DR development.

Clinical Implications of MiR128, Angiotensin I Converting Enzyme and Vascular Endothelial Growth Factor Gene Abnormalities and Their Association with T2D.

Type 2 DM (T2D) results from the interaction of the genetic and environmental risk factors. Vascular endothelial growth factor (VEGF), angiotensin I-converting enzyme (ACE), and MicroRNAs (MiRNAs) are involved in important physiological processes. Gene variations in VEGF, ACE and MiRNA genes are associated with diseases. In this study we investigated the associations of the VEGF-2578 C/A (rs699947), VEGF-2549 insertion/deletion (I/D), and ACE I/D rs4646994 and Mir128a (rs11888095) gene variations with T2D using the amplification refractory mutation system PCR (ARMS-PCR) and mutation specific PCR (MSP). We screened 122 T2D cases and 126 healthy controls (HCs) for the rs699947, and 133 T2D cases and 133 HCs for the VEGF I/D polymorphism. For the ACE I/D we screened 152 cases and 150 HCs, and we screened 129 cases and 112 HCs for the Mir128a (rs11888095). The results showed that the CA genotype of the VEGF rs699947 and D allele of the VEGF I/D polymorphisms were associated with T2D with OR =2.01, p-value = 0.011, and OR = 2.42, p-value = 0.010, respectively. The result indicated the D allele of the ACE ID was protective against T2D with OR = 0.10, p-value = 0.0001, whereas the TC genotype and the T allele of the Mir128a (rs11888095) were associated with increased risk to T2D with OR = 3.16, p-value = 0.0001, and OR = 1.68, p-value = 0.01, respectively. We conclude that the VEGF (rs699947), VEGF I/D and Mir128a (rs11888095) are potential risk loci for T2D, and that the D allele of the ACE ID polymorphism may be protective against T2D. These results help in identification and stratification for the individuals that at risk for T2D. However, future well-designed studies in different populations and with larger sample sizes are required. Moreover, studies to examine the effects of these polymorphisms on VEGF and ACE proteins are recommended.

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.

The association of VEGF rs833061 and rs2010963 polymorphisms with susceptibility to colorectal cancer in an Iranian population

Vascular endothelial growth factor (VEGF) is one of the most important regulators of angiogenesis. Several single nucleotide polymorphisms (SNPs) are associated with the VEGF overexpression and tumor progression in several cancers. This study aimed to determine the association of VEGF rs833061 and rs2010963 polymorphism and their haplotypes with susceptibility to colorectal cancer (CRC) in the Iranian population. A total of 284 colorectal cancer patients (37.3% women, 62.7% men) were enrolled in this study. Healthy controls without evidence of cancer history or family cancer predispositions were frequency-matched to the cases by sex and age (± 5 years). Genotyping was performed by the Sequenom mass ARRAY method and the genotype distribution and risk estimate were analyzed by SPSS software. The correlation between the genotypes and clinicopathological parameters (Dukes stage, phenotype, location, differentiation, and tumor size) among colorectal cancer patients were investigated. We found a significant relationship, between rs833061T/C genotype and their TG haplotype with the age of diagnosis < 60; (p = 0.012, p = 0.014) and rs2010963G/C genotype with female gender and TG haplotype with third and fourth tumor stage and tumor location (p = 0.04and p = 0.047). This study showed that rs833061T/C genotype and TG haplotype increase the susceptibility to colon cancer in the Iranian population. This susceptibility has a significant relationship with the age of diagnosis and different stages of the tumor.

MO1019ASSOCIATION OF VEGF ANF TGF1 GENES POLYMORPHISMS WITH SERUM CONCENTRATION OF GENE PRODUCTS IN CHILDREN WITH LUPUS NEPHRITIS

Abstract Background and Aims Previously it was shown that significantly elevated serum concentration of vascular-endothelial growth factor (VEGF) and transforming growth factor β (TGF-β1) is observed in Lupus Nephritis (LN) patients, especially in those with disease exacerbation. In this study we investigated the association of selected single nucleotide polymorphisms (SNP) in TGF-β1 and VEGF genes with serum concentration of the gene product in children with LN. Method We enrolled 22 children with LN (m:f 2/20) aged 10 to 17 years. Blood samples were taken twice in every child – in remission and during exacerbation of the disease. Serum concentration of VEGF and TGF-β1 was measured using R&amp;D Systems Quantikine ELISA “Human TGF-β1” and “VEGF” kits. DNA was analyzed by polymerase chain reaction for identification of selected SNPs – VEGF rs699947 (A/C), rs2010963 (G/C), TGF-β1 rs1800469 (G/A). Results We didn’t find any association of serum concentration of TGF-β1 with rs1800469 polymorphism in individuals with LN in exacerbation and in remission either (p&amp;gt;0,05). Concentration of VEGF was associated with genotypes of VEGF gene. It was significantly higher in LN patients harboring AA genotype for rs699947 comparing with those with CC+CA group of genotypes (ie carrying at least one minor allele A). This association was observed in exacerbation period (p&amp;lt;0,001), but not in remission (p&amp;gt;0,05). We compared major genotype GG and group of genotypes GC+CC (ie patients with at least one minor allele C) of VEGF gene (rs2010963). It was found that statistically significant elevation of gene product was found in individuals with group of genotypes GC+CC in exacerbation period (p=0,036). In remission concentration of the gene product didn't differ in patients with GG and GC+CC genotypes (p=0,97). VEGF gene genotypes rs699947 and rs2010963 are in high linkage disequilibrium (LD). Having analyzed combined genotypes we found that association with the gene product was the same as in rs699947 alone analysis. This may suggest functional importance of this SNP. Rs2010963 more likely to show association with the gene product due to linkage with rs699947. Conclusion There is an association between VEGF gene genotypes (rs699947 and rs2010963) and gene product serum concentration in LN pediatric patients in exacerbation period. Among two investigated loci of VEGF gene rs699947 might be considered more relevant risk marker of VEGF disfunction. No statistically significant association was found in our study for TGF-β1 gene genotypes (rs1800469) and its' product serum concentration.

The role of VEGF rs699947 polymorphism in End-Stage Renal Disease: A preliminary study

Aim: End-Stage Renal Disease (ESRD) is an important public health problem worldwide with an increasing incidence and prevalence. There are many environmental and genetic factors which contribute to the development of ESRD. Vascular endothelial growth factor (VEGF) has been suggested to play an important role in renal pathophysiology. The aim of this study was to determine the probable relation between ESRD and VEGF gene rs699947 polymorphism in Turkish population. Material and Method: Genotyping of rs699947 was carried out in 50 ESRD patients on dialysis treatment and 30 healthy controls, using a Kompetitive Allelic-Specific PCR (KASP) method following DNA isolation. Demographic and clinical characteristics of the patients were recorded. Results: The prevalance of rs699947 AA genotype was found to be higher in the control group, but it was not statistically significant (p&gt;0.05) . Conclusion: Although statistically insignificant, the frequency of AA genotype was higher in the control group compared to the case group, therefore we concluded that AA genotype may be a protective factor for ESRD in Turkish population. However, this conclusion needs to be further verified by future studies performed in larger study groups.

Methylene tetrahydrofolate reductase (MTHFR) and vascular endothelial growth factor (VEGF) polymorphisms in Brazilian patients with Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC)

OBJECTIVE:The folate pathway is involved in hepatic carcinogenesis and angiogenesis. Polymorphisms in genes related to such processes, including methylene tetrahydrofolate reductase (MTHFR) and vascular endothelial growth factor (VEGF)] may play an important role in the development of hepatocellular carcinoma (HCC). The objective of this study was to evaluate MTHFR and VEGF polymorphisms in Brazilian patients with hepatitis C virus (HCV)-related HCC.METHODS:A total of 119 patients diagnosed with confirmed HCC and HCV were included in the study. SNP genotyping assays were performed using real-time PCR. VEGFA (rs2010963, rs3025039, and rs833061) and MTHFRC677T (rs1801133, rs1801131) polymorphisms were evaluated.RESULTS:The C alleles of MTHFR (rs1801131) and VEGF (rs2010963) were associated with protection against the development of multinodular HCC, while the T allele of MTHFR (rs1801133) was associated with a higher risk of multinodular presentation [p=0.04 OR 1.835 CI (1.022-3.297)]. Multivariate analysis revealed that the GG/GC genotypes of VEGF rs2010963 were independently associated with multinodular tumors at diagnosis (p=0.013; OR 4.78 CI (1.38-16.67)].CONCLUSION:Our results suggest that these polymorphisms may increase the risk of rapid tumor progression in patients with HCV infection. This subgroup of patients with HCC and who present polymorphism is more likely to be diagnosed with multinodular disease and not be amenable to receiving curative treatments. These data must be validated in larger cohorts, and the screening intervals can be customized based on genetic history.

Genetic factors and the presence of coronary collaterals in patients with stable coronary artery disease

Abstract Background The coronary collateral circulation (CCC) varies in patients with coronary artery disease (CAD). Although many studies were provided to detect factors associated with collateral development, genetic factors are still studied insufficiently. The goal of this study was to assess the association of single nucleotide polymorphisms (SNP) in genes involved in vascular growth with CCC in patients with stable CAD. Purpose To assess if genetic variations in hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), urokinase-type plasminogen activator (gene PLAU) are associated with the presence of coronary collaterals in patients with stable CAD. Methods A single-centered study was performed between March 2012 and December 2017. In 579 patients with stable CAD who underwent coronary angiography and had at least 50% stenosis in at least one major coronary artery collaterals were assessed by the use of the Rentrop score (0–3) during coronary angiography. SNPs PLAU rs4065, VEGF rs1570360, rs2010963 and rs699947, HGF rs5745752 were genotyped, multivariate logistic regression was carried out to determine the association of genotypes with CCC. Results 337 patients had visible coronary collaterals (Rentrop grade 1, 2 and 3) and 236 patients didn't have visible collaterals (Rentrop grade 0). Beside traditional risk factors of poor CCC - diabetes, smoking and arterial hypertension – patients without visible coronary collaterals (Rentrop 0) showed a higher frequency of the HGF rs5745752 CC genotype than those with visible coronary collaterals (Rentrop 1–3; p=0.001). (Fig. 1) The odds ratio of having CCC Rentrop 0 in patients with genotype CC was statistically significant (odds ratio = 1.94 [95% confidence interval: 1.38–2.76]; p=0.001). Statistical analysis showed that the PLAU rs4065 and VEGF rs1570360, rs2010963 and rs699947 polymorphisms were not associated with CCC (p&amp;lt;0.05). Conclusion An association was found between the HGF rs5745752 polymorphism and the CCC in patients with stable CAD. Patients with the CC genotype are at greater risk of developing poor coronary collaterals. Figure 1 Funding Acknowledgement Type of funding source: None

Genetic association of vascular endothelial growth factor (VEGF) gene variants with the risk for diabetic retinopathy: a meta-analysis

The vascular endothelial growth factor (VEGF) significantly contributes to the manifestation of neovascularization in the retina which progressively develops retinopathy in diabetic patients. The aim of this study was to assess the role of VEGF polymorphisms in the pathogenesis of diabetic retinopathy (DR). This meta-analysis comprised a total of six case-control and cohort studies published in the last 6 years. The selection of studies was done by sorting in reliable database searches: NCBI, Ensemble, GenBank, Embase, UCSC Genome Browser. After the extraction of data, the Q test of heterogeneity was performed. The Stata Software version 13.1 was used as the statistical package. Fixed and random effect models were applied for forest plot depiction while funnel plot and Egger’s test were carried out for the evaluation of publication bias. A significant relationship was found between the risk allele of VEGF polymorphism rs3025039 with predisposition of DR (OR = 1.45, 95%CI = 1.04–1.86) in the absence of heterogeneity by three studies. Furthermore, significant association was also observed for four polymorphisms of VEGF (rs833061, s13207351, rs1570360, and rs2010963) with higher susceptibility of DR among the population of Pakistan (OR = 1.46, 95%CI = 1.21–1.71). The meta-analysis suggested the substantial role of VEGF polymorphism rs3025039 as a possible biomarker for the assessment of DR risk. However, genome-wide association study (GWAS) is required in future to elucidate the multi-SNP effect of these polymorphisms in VEGF gene.

Association of Genetic Variants in ANGPT/TEK and VEGF/VEGFR with Progression and Survival in Head and Neck Squamous Cell Carcinoma Treated with Radiotherapy or Radiochemotherapy.

Angiogenesis is essential for growth, progression, and metastasis of solid tumors. Vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) and angiopoietin (ANGPT)/ tyrosine kinase endothelial (TEK) signaling plays an important role in regulating angiogenesis. Very little is known about the effects of single-nucleotide polymorphisms (SNPs) in angiogenesis-related genes on treatment outcome in head and neck squamous cell carcinoma (HNSCC). Therefore, we evaluated the association between SNPs in ANGPT1, ANGPT2, TEK, VEGF, VEGFR1, and VEGFR2 genes and five clinical endpoints in 422 HNSCC patients receiving radiotherapy alone or combined with chemotherapy. Multivariate analysis showed an association of ANGPT2 rs3739391, rs3020221 and TEK rs639225 with overall survival, and VEGF rs2010963 with overall and metastasis-free survival. VEGFR2 rs1870377 and VEGF rs699947 affected local recurrence-free survival in all patients. In the combination treatment subgroup, rs699947 predicted local, nodal, and loco-regional recurrence-free survival, whereas VEGFR2 rs2071559 showed an association with nodal recurrence-free survival. However, these associations were not statistically significant after multiple testing correction. Moreover, a strong cumulative effect of SNPs was observed that survived this adjustment. These SNPs and their combinations were independent risk factors for specific endpoints. Our data suggest that certain germline variants in ANGPT2/TEK and VEGF/VEGFR2 axes may have predictive and prognostic potential in HNSCC treated with radiation or chemoradiation.

Genetic variants of vascular endothelial growth factor gene polymorphism affect the risk and severity of ischemic stroke: a case–control study

<br><b>Background and objectives</b><br>Vascular endothelial growth factor (VEGF) is the key mediator of angiogenesis and atherosclerosis. Hence, it may play a major role in the pathogenic mechanisms underlying ischemic stroke (IS) progression. Thus, we conducted this case–control study to explore the genetic association of a single gene polymorphism of VEGF + 936C/T (rs3025039) with the risk and severity of IS and its relation with serum VEGF level.<br><b>Patients and methods</b><br>This study included a case series of 49 patients with IS with 41 controls. VEGF + 936C/T (rs3025039) variants were determined via Taqman allelic discrimination PCR. Serum VEGF level was estimated using enzyme-linked immunosorbent assay. The frequency of VEGF rs3025039 genotypes and alleles was calculated manually in both cases and controls. The risk ratio was estimated and represented by odds ratio (OR) and 95% confidence interval (CI) adjusted to the confounding variables via multinomial logistic regressions. The stroke severity was assessed by National Institute of Health Stroke Scale. Moreover, serum VEGF levels were compared between the studied groups and among different genotypes and alleles of IS cases.<br><b>Results</b><br>Our study detected significantly increased frequencies of TT genotype (<i>P</i> = 0.030) and T allele (<i>P</i> = 0.045) in IS cases when compared with the controls. TT genotype represents an increased adjusted risk for IS progression by 9.94 folds (OR: 9.938, 95% CI: 1.235–79.97) and T allele by 2.19 folds (OR: 2.191, 95% CI: 1.004–4.782) over the CC genotypes and C allele, respectively. Moreover, TT genotypes are associated with higher National Institute of Health Stroke Scale. The serum VEGF level was significantly lower in IS cases than controls, and a more decreased level was associated with the T allele carriers in IS cases groups.<br><b>Conclusions</b><br>VEGF rs3025039 gene polymorphism is associated with increased risk and severity of IS and decreased VEGF expression, which may play a major role in the pathogenesis of IS progression.<br>

Associations between twelve common gene polymorphisms and susceptibility to hepatocellular carcinoma: evidence from a meta-analysis

BackgroundAssociations between polymorphisms in vitamin D receptor (VDR)/vascular endothelial growth factor (VEGF)/interleukin-18 (IL-18)/mannose-binding lectin (MBL) and susceptibility to hepatocellular carcinoma (HCC) were already explored by many studies, yet the results of these studies were inconsistent. The aim of this meta-analysis was to better clarify associations between polymorphisms in VDR/VEGF/IL-18/MBL and HCC by combing the results of all relevant studies.MethodsEligible publications were searched from PubMed, Embase, WOS, and CNKI. We used Review Manager to combine the results of individual studies.ResultsThirty studies were included in this study. Combined results revealed that VDR rs7975232, VDR rs2228570, VEGF rs699947, VEGF rs3025039, IL-18 rs1946518, and MBL rs7096206 polymorphisms were all significantly associated with HCC in the overall pooled population. We also obtained similar significant associations for VDR rs7975232, VDR rs2228570, IL-18 rs1946518, and MBL rs7096206 polymorphisms in Asians.ConclusionsCollectively, this meta-analysis proved that VDR rs7975232, VDR rs2228570, VEGF rs699947, VEGF rs3025039, IL-18 rs1946518, and MBL rs7096206 polymorphisms may confer susceptibility to HCC in certain populations.