Vascular Endothelial Growth Factor Genotypes Research Articles

Efficiency of Vascular Endothelial Growth Factor-2549 Insertion/Deletion variation and VEGF level to predict Retinopathy in Diabetes Mellitus Type 2 Cases

The current work was suggested to study Vascular Endothelial Growth Factor (VEGF) level and VEGF -2549 Insertion/Deletion (I/D) to predict retinopathy in Diabetes Mellitus type 2 cases. Three groups were used to implement the study aim: Diabetes Mellitus type 2 (DM) with and without retinopathy and healthy individuals. Glycemic parameters, VEGF level and VEGF -2549 (I/D) were involved in the present study. The findings demonstrated that there were significant differences between DM cases and control in all glycemic biomarkers. The VEGF level (p<0.001) in DM with retinopathy significant elevation was shown VEGF level (p=0.047) and non-sig changes were observed in other parameters. The VEGF -2549 (I/D) showed non-significant association (p=0.245) of allele (I, D) in study groups while significant association (p=4.44e-04) was observed in DM with and without retinopathy. The genotypes of VEGF -2549 (I/D) showed low frequents of heterozygote (I/D) in case-control groups and slight changes in (D/D) and (I/I) (P=0.603). significant association of (I/I) with DM with retinopathy was observed while D/D was associated with DM without retinopathy group (P= 0.034). The effect of VEGF -2549 (I/D) in study biomarkers showed non-sig changes in case and control groups in all parameters (beta =-1.421, p= 0.999), while in DM with and without retinopathy, biomarkers showed non-sig differences association by regression test (beta =0.865, p=0.999). From the present results, it can be proposed that VEGF level was elevated in DM with retinopathy, VEGF -2549 (I/D) was significantly associated with DM with retinopathy and may be used to predict retinopathy in DM.

Association Between Vascular Endothelial Growth Factor (VEGF) +936C/T Polymorphism (rs3025039) and Preeclampsia Among Myanmar Pregnant Women.

Background: The vascular endothelial growth factor (VEGF) polymorphism is associated with preeclampsia since its abnormal expression plays an important role in vasculogenesis in placenta formation. Thus, this study is aimed at analyzing the association between VEGF +936C/T polymorphism and the risk of preeclampsia. Methods: To assess the causal relationship, a hospital-based cross-sectional analytical study was carried out among 204 Myanmar pregnant women during the period of January 2018-September 2020. For data collection, a pretested, structured questionnaire was used. Blood samples were collected after obtaining consent, and then we studied the extracted gene by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The Statistical Package for Social Sciences version 18.0 was used for data management and analysis. Results: The genotype CT variant among preeclamptic women was more than that of non-preeclamptic women (26.5% vs. 18.6%), but not significant (p = 0.180). The risk of preeclampsia among women with CT genotypes was 1.57 times higher than that of women with CC genotypes (OR (95%CI) = 1.57 (0.81, 3.06), p = 0.180). The minor allele frequency of the T allele was 15.2% in preeclamptic women and 9.3% in normal pregnant women. The risk of preeclampsia among T allele carriers is 1.49 times (95%CI = 0.80, 2.77) more than that of C allele carriers (p = 0.211). Among the preeclamptic pregnant women, the frequency of the CT genotype was 26.3% in the severe preeclamptic group and 26.9% in the mild preeclamptic group, while the frequency of the T allele was 13.2% and 13.5%, respectively. The frequency of either CT genotype or T allele was more or less the same in both groups, and there was no association between VEGF C/T polymorphism and the severity of preeclampsia. After logistic regression analysis on VEGF genotype and clinical parameters such as age, maternal body mass index (BMI), and neonatal birth weight, the risk of preeclampsia was 2.1 times higher in pregnant women with CT genotype compared to CC genotype (adjusted OR, 2.1; 95% CI, 0.9-4.5, p value -0.057). Conclusion: There was no significant association between VEGF +936C/T polymorphism (rs3025039) and preeclampsia among Myanmar pregnant women. However, the findings of this study highlighted that individuals carrying either the CT genotype or the T allele are at a heightened risk of developing preeclampsia. Furthermore, it suggests a potential impact of the gene on the occurrence of preeclampsia, yet the data lacks sufficient evidence to establish statistical significance.

VEGF and eNOS variants may influence intervertebral disc degeneration

Background: Intervertebral disc degeneration (IDD) is a common and complex condition. Vascular endothelial growth factor (VEGF) is one of the key regulators of angiogenesis and vascular permeability. Nitric oxide (NO) plays a role in various physiological events. The endothelial nitric oxide synthase (eNOS) that catalyses NO generation are crucial for the regulation of NO level. This study aimed to evaluate the association between VEGF/ eNOS gene variants with IDD. Materials and Methods: Two hundred ninety-one subjects (111 IDD patients and 180 controls) were included in the present case-control study. VEGF −2549 insertion/deletion (I/D) and eNOS VNTR variants were analysed by PCR method. The results of this analysis were evaluated for statistical significance. Results: There were no statistically significant differences in genotype and allele distribution of VEGF −2549 I/D/ eNOS VNTR variants between IDD patients and control subjects. We then evaluated the association between the allele frequencies of these variants and clinical features of IDD. Lumber IDD was more common in patients carrying VEGF I/D variant D allele (p < 0.001). Also, patients with lumbar disc herniation, cervical disc herniation, lumbar stenosis, and lumbar IDD had more 4 b allele (p = 0.005, p < 0.001, p < 0.001, and p = 0.03, respectively). Conclusions: In conclusion, this study demonstrates first time that some clinical characteristics of IDD have been associated with allele frequencies of VEGF −2549 I/D/ eNOS VNTR variants.

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

Association of VEGF -2549 I/D and VEGF +936 C/T Polymorphisms with Chronic Kidney Disease in North-West Indian Patients.

Chronic kidney disease (CKD) is a complex multifactorial disease in which both genetic and environmental factors influence the onset, development and progression of disease. The genetic variations in the vascular endothelial growth factor (VEGF) can influence levels of VEGF protein expression, and thus, susceptibility to progression of kidney diseases. The aim of the present study was to evaluate the association of VEGF-2549 I/D and VEGF +936 C/T polymorphisms in CKD stage V patients from North-West India. In this case-control study, 166 patients and 166 controls were analyzed. DNA samples were screened for VEGF -2549I/D and VEGF +936 C/T polymorphisms using polymerase chain reaction-based (PCR) methods. The genotype frequency of VEGF -2549 I/D was significantly different between patients and controls (P < 0.05). ID genotype of VEGF -2549 I/D polymorphism was significantly associated with decreased risk of CKD (P = 0.009). Genetic model analysis of VEGF -2549 I/D polymorphism revealed a significantly decreased risk of CKD in co-dominant (P = 0.009), dominant (P = 0.021), and over-dominant (P = 0.012) models. Genotype and allele frequency of VEGF +936 C/T polymorphism was not significantly different between the patient and control groups. Genotype combination analysis revealed that ID-CT genotype combination of VEGF -2549 I/D and VEGF +936 C/T polymorphisms was associated with decreased CKD risk (P = 0.047). VEGF -2549 ID genotype and ID-CT genotype combination of VEGF -2549 I/D and VEGF +936 C/T polymorphisms was significantly associated with reduced CKD risk in North-West Indians.

Vascular endothelial growth factor haplotypes are associated with severe ischaemic complications in giant cell arteritis regardless of the disease phenotype.

To determine whether functional vascular endothelial growth factor (VEGF) polymorphisms influence the expression of the clinical phenotype of giant cell arteritis (GCA). We also evaluated whether VEGF polymorphism is associated with the development of severe ischaemic manifestations in patients with GCA regardless of the clinical phenotype, classic cranial GCA or predominantly extracranial GCA large vessel vasculitis (LVV). VEGF rs833061 T/C, rs2010963 G/C and rs3025039 C/T polymorphisms were genotyped in 185 patients with biopsy-proven cranial GCA, 105 with extracranial LVV-GCA and 490 healthy controls. Allelic combinations (haplotypes) of VEGF were carried out. Comparisons were performed between patients with GCA and healthy controls as well as between patients with GCA stratified according to the clinical phenotype and the presence of severe ischaemic manifestations. No significant differences in genotype, allele, and haplotype frequencies of VEGF were found between patients with GCA and healthy controls as well as between GCA patients with the classic cranial pattern and the extracranial LVV-GCA pattern of the disease. However, the VEGF CGC haplotype (OR= 1.63 [1.05-2.53]) and the CGT haplotype (OR= 2.55 [1.10-5.91]) were significantly more frequent in GCA patients with severe ischaemic complications compared to those patients without these complications. VEGF haplotypes seem to play a role in the development of severe ischaemic manifestations in GCA patients, regardless of the clinical phenotype of expression of the disease.

Association of -634 C/G Polymorphism at Vascular Endothelial Growth Factor Gene with Risk Retinopathy of Prematurity

Background: Retinopathy of prematurity (ROP) is a major cause of blindness in newborn infants worldwide. It is well known that neovascularization of the retina is prominent in the proliferative stages of ROP. It is suggested that vascular endothelial growth factor (VEGF) may play a role in the development of ROP. The aim of this study was to evaluate the association of the VEGF -634C/G polymorphism at VEGF with risk of ROP. Methods: In the study 54 neonates diagnosed with ROP and 55 healthy neonates served as controls. The VEGF -634 C/G polymorphism was genotyped by restriction fragment length polymorphism (PCR-RFLP) technique. Results: The CC, CG, and GG genotypes of VEGF -634C/G polymorphism were found in 33.3%, 38.9%, and 27.8% of neonates with ROP, respectively. In controls, CC, CG, and GG genotypes were seen in 43.6%, 45.4%, and 10.9%, respectively. Frequency of mutant allele (C) was 52.8% in neonates with ROP and 66.4% in healthy neonates. There was a significant difference in the distribution of VEGF -634C/G polymorphisms between cases and controls. Moreover, there was a significant association between VEGF -634C/G polymorphisms and ROP risk (OR = 3.141, 95% CI 1.115-8.851, P = 0.030). Conclusion: This study results revealed that VEGF -634C/G polymorphism might serve as a risk factor for development of ROP. Thus, clinicians should be aware of the ROP risk in infant with the VEGF -634C/G polymorphism and ROP risk in infants. However, large sample size and well-designed studies are necessary to validate our findings.

Association of Single-Nucleotide Polymorphism (rs833061) of Vascular Endothelial Growth Factor with Breast Cancer Risk

Background: Breast cancer is the most common cancer among women and one of the most important causes of death among them. Angiogenesis is an important step for primary tumor growth, invasiveness, and metastases. Vascular endothelial growth factor (VEGF) is involved in angiogenesis associated with tumors. Objective: To investigate the association of single nucleotide polymorphisms (SNPs) of VEGF gene located in the promoter region at position 460T/C (rs833061) with the risk of breast cancer. Patients and Methods: This study was conducted on (40) Egyptian female patients who were diagnosed as breast cancer according to histopathological examination of breast biopsy (Group 1, Patients), in addition to (40) age-matched apparently healthy females serving as controls (Group II, Controls). Detection of SNP of VEGF gene located in the promoter region 460T/C (rs833061) was done by real-time polymerase chain reaction technique. Results: There was no significant difference in frequency of the (C/C, T/C and T/T) genotypes of VEGF 460T/C (rs833061) in group I compared with group II (p>0.05). None of the studied VEGF genotypes had shown significant difference in distribution related to clinico-pathological parameters as tumor size, histological grade, hormone receptors, HER2/new status, regional lymph node and distant metastasis (p>0.05). Conclusion: This study revealed that there was no significant association of the (C/C, T/C and T/T) genotypes of VEGF 460T/C (rs833061) and breast cancer risk. Moreover, VEGF polymorphism 460T/C (rs833061) was not associated with breast cancer patients’ clinico-pathological characteristics and tumor markers levels.

Influence of polymorphisms in VEGF, TNF-α, and GSTP1 genes on retinopathy of prematurity risk: a Meta-analysis

Purpose To investigate the influence of polymorphisms in vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), and glutathione S-transferase Pi isoform (GSTP1) genes on retinopathy of prematurity (ROP) risk, we performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant meta-analysis. Methods An exhaustive search was conducted in PubMed, Web of Science, and CNKI for genetic studies evaluating the relationship between VEGF (−460 T/C, +936 C/T, −634 G/C, and −2578 C/A), TNF-α (−308 G/A) and GSTP1 (Ile/Val) polymorphisms and ROP risk from inception until November 2019. Odds ratio (OR) with the 95% confidence interval (CI) were used for estimating combined effect size. The quality of the included studies was evaluated using the Newcastle-Ottawa Scale (NOS). Results A total of 14 studies met the inclusion criteria. The meta-analyses revealed that VEGF − 460 T/C was associated with ROP risk in the allele model (C vs. T, OR = 0.83, 95% CI: 0.74–0.94, POR=0.004), homozygous gene model (CC vs. TT, OR = 0.70, 95% CI: 0.54–0.91, POR=0.008), dominant gene model (CC + TC vs. TT, OR = 0.80, 95% CI: 0.67–0.95, POR = 0.012), and recessive gene model (CC vs. TC + TT, OR = 0.74, 95% CI: 0.59–0.94, POR = 0.014). However, we did not find significant differences in the genotype and allele distribution of VEGF + 936 C/T, −634 G/C, −2578 C/A, TNF-α − 308 G/A and GSTP1 Ile/Val polymorphisms, between ROP and control group (p > .05). Conclusions VEGF polymorphism −460 T/C was associated with a lower ROP risk. Further research is warranted to investigate haplotype effects of VEGF polymorphisms on the risk of ROP.

The association of vascular endothelial growth factor polymorphism (rs699947) with diabetic foot ulcer and oxidative status

BackgroundDiabetic foot ulcer (DFU) is a common, complex, and costly complication of diabetes that affects the lower extremities. Foot ulceration is the most frequently recognized issues in this disease. The vascular endothelial growth factor (VEGF), encompassing 14 kb, is located on chromosome 6p21.3, and contains 8 exons and 7 introns. There are at least 25 different single nucleotide polymorphisms (SNPs) in the VEGF that are associated with DFU, the current study deals with the most frequent and important one, the rs699947. ObjectiveTo investigate the molecular basis of the SNP (rs699947) (-2578C>A) and its correlation with biochemical parameters, such as HbA1c, GSH and MDA, in patients with DFU, in the Kerbala province of Iraq. Materials and methodsThis study was a cross-sectional study, including 240 subjects of both sexes, which are randomly selected. Subjects were divided into two groups, 120 had DFU and 120 had type 2 diabetes (T2DM), as a control group.The VEGF genotyping was performed by the amplification refractory mutation system- Polymerase Chain Reaction (ARMS-PCR) of DNA, extracted from peripheral blood mononuclear cells of 120 unrelated patients, and 120 unrelated control donors. ResultsThe VEGF polymorphism (rs699947) has a significant association with DFU. The AC genotype significantly raised the risk of DFU (p value ≤ 0.01), but the C allele was more effective in this increase (p value ≤ 0.01).The correlation of AA, AC and CC genotypes of the VEGF polymorphism (rs699947) with biochemical parameters, such as HbA1c, GSH and MDA was significant (p value ≤ 0.01), comparing patients with DFU, and T2DM as a control group. ConclusionA significant association was found between the VEGF polymorphism (rs699947) and DFU, in comparison with the T2DM, as a control group.

Analysis of VEGF gene polymorphisms and serum VEGF protein levels contribution in polycystic ovary syndrome of patients.

Vascular endothelial growth factor (VEGF) is a well-known factor in reproductive function and contributes to the pathogenesis of polycystic ovary syndrome (PCOS). Genetic variations in VEGFA gene were suggested to contribute alterations in VEGF secretion and PCOS. This study evaluated the association of VEGFA SNPs with altered VEGF secretion level and PCOS among ethnically-matched control women. This prospective case-control study was conducted from 2016 to 2018 and comprised of 55 women with PCOS and 52 control subjects. ELISA was used to measure VEGF levels; and various other related bio chemicals whereas the genotyping of VEGFA variants was performed through the analysis of nine SNPs of VEGF. PRL, E2, PRGE testosterone and glucose level were found to be insignificantly different. The levels of FSH, LH, LH/FSH, TT, insulin, SHBG and HOMA-IR were significantly higher in the study group. Among the nine tested variants of VEGF SNPs, two SNPs rs3025020 and rs833061, consisted of TT (Recessive and Dominant homozygous, respectively) which were marginally higher in test. The SNP rs1570360 had significantly higher GG allele (32.73%) which was recessive homozygous. There was no significant difference observed in genotype frequencies related to higher value of VEGF. The genotype frequencies for the studied SNPs were in alignment with Hardy-Weinberg equilibrium (HWE). The mean serum VEGF levels got significantly increased in PCOS group. No significant association was found between VEGF genotypes and its serum levels. VEGF levels in rs699947 (AA-major homozygous), rs3025039 (CC-major homozygous) and rs833061 (TT & CC-major & minor homozygous) genotypes were significantly higher in PCOS. The study results evidently proved that the allelic variants in genes may be a factor for PCOS and VEGF serum levels with respect to few SNP variants only. These findings indicated that VEGF may be involved in PCOS status and confirmed the previous association between genetic variants in VEGF, serum level of VEGF protein and PCOS.

Association of vascular endothelial growth factor expression and polymorphisms with the risk of gestational diabetes mellitus.

To study the associations of vascular endothelial growth factor (VEGF) expression and its gene polymorphisms with the risk of gestational diabetes mellitus (GDM). A total of 239 GDM patients (GDM group) and 275 healthy pregnant women (Control group) were included in this study. VEGF genotypes (including rs2146323, rs2010963, rs3025039, rs3025010, and rs833069) were analyzed by TaqMan assay. ELISA was used to determine the serum VEGF levels. The software SHEsis was performed to analyze haplotypes. The carrier with the rs2146323 AA, CA+AA genotypes, and A allele, as well as the rs3025039 CT, TT, CT+TT genotypes, and T allele showed the increased risk of GDM (all P<0.05), but the distributions of genotype and allele at rs2010963, rs3025010, and rs833069 were not significantly different between GDM patients and controls (all P>0.05). Notably, the frequency of rs2010963-rs833069-rs2146323-rs3025010 haplotypes CAAC, CAAT, CACC, CACT, GACT, and GGCT was found statistically different between GDM patients and controls (all P<0.05). The patients with rs3025039 CT+TT genotype had higher VEGF levels than those with CC genotype (all P<0.05). Besides, age, family histories of diabetes, previous GDM, hypertension, pre-pregnancy body mass index, fasting plasma glucose, fasting insulin, homeostasis model assessment (HOMA)-IR, rs2146323 CA+AA, rs3025039 CT+TT, and VEGF expression level were independent risk factors, while HOMA-β was an independent protective factor for GDM (all P<0.05). VEGF rs2146323 and rs3025039 polymorphisms and its expression were significantly correlated with the risk of GDM, providing a great clinical value for GDM assessment and diagnosis.

Vascular Endothelial Growth Factor (VEGF) Polymorphisms and Serum VEGF Levels in Women With Epithelial Ovarian Cancer, Benign Tumors, and Healthy Ovaries.

This study analyzed the relation of 5 single-nucleotide polymorphisms (SNPs) in the VEGF (vascular endothelial growth factor) gene in patients with epithelial ovarian cancer (EOC), compared with patients carrying benign tumors or healthy ovaries. We studied serum VEGF levels and the relation with SNPs and association between VEGF SNPs and haplotypes with progression-free survival (PFS) in patients with cancer. The genotyping of VEGF gene polymorphisms (-2578 C/A, -1154 G/A, -460 T/C, +405 G/C, +936 C/T) was performed in DNA isolated from blood samples of 100 women. The different genotypes were evaluated by quantitative real-time polymerase chain reaction. Vascular endothelial growth factor protein concentration was assessed in serum using solid-phase sandwich enzyme-linked immunosorbent assay. We found statistically significant differences in the distribution of VEGF genotypes among the 3 groups of patients: -2578 C/A between those with EOC and healthy ovary (P = 0.04), -460 T/C between those with EOC and healthy ovary (P = 0.03), and -460 T/C between those with benign tumors and healthy ovary (P = 0.02). Vascular endothelial growth factor serum levels were analyzed in patients with EOC. Higher levels were found in patients with clear cell carcinoma compared with those with serous, mucinous, or endometrioid tumors (P < 0.05). No clear association was observed between VEGF SNPs and serum VEGF levels. There was no significant correlation between VEGF SNPs and PFS. In haplotype analysis, CGTCT and CGTGT showed worse prognosis without reaching the statistical significance. CGCGC and AGTGC haplotypes had statistically significant differences among patients with EOC, benign tumors, and healthy ovaries (Ps = 0.046 and 0.041, respectively). The distribution of VEGF genotypes was different in patients with EOC, compared with those with benign tumors or women with healthy ovaries. Vascular endothelial growth factor serum levels were higher in patients with clear cell carcinoma. No correlation was found with improved PFS, but CGTCT and CGTGT haplotypes showed worse prognosis.

Ethnic differences in the +405 and \u2212460 vascular endothelial growth factor polymorphisms and peripheral neuropathy in patients with diabetes residing in a North London, community in the United Kingdom

BackgroundThere are marked ethnic differences in the susceptibility to the long-term diabetic vascular complications including sensory neuropathy. The vascular endothelial growth factor (VEGF) +405 (C/G) and −460 (T/C) polymorphisms are associated with retinopathy and possibly with nephropathy, however no information is available on their relationship with peripheral neuropathy. Therefore, we examined the prevalence of these VEGF genotypes in a multi-ethnic cohort of patients with diabetes and their relationship with evident peripheral diabetic neuropathy.MethodsIn the current investigation, we studied 313 patients with diabetes mellitus of African-Caribbean, Indo-Asian and Caucasian ethnic origin residing in an inner-city community in London, United Kingdom attending a single secondary care centre. Genotyping was performed for the VEGF +405 and VEGF −460 polymorphisms using a pyrosequencing technique.ResultsForty-nine patients (15.6%) had clinical evidence of peripheral neuropathy. Compared to Caucasian patients, African-Caribbean and Indo-Asian patients had lower incidence of neuropathy (24.6%, 14.28%, 6.7%, respectively; P = 0.04). The frequency of the VEGF +405 GG genotype was more common in Indo-Asian patients compared to African-Caribbean and Caucasian patients (67.5%, 45.3%, 38.4%, respectively; p ≤ 0.02). The G allele was more common in patients with type 2 diabetes of Indo-Asian origin compared to African-Caribbean and Caucasian origin (p ≤ 0.02). There was no difference between the ethnic groups in VEGF −460 genotypes. The distributions of the VEGF +405 and VEGF −460 genotypes were similar between the diabetic patients with and without neuropathy.ConclusionsIn this cohort of patients, VEGF +405 and VEGF −460 polymorphisms were not associated with evident diabetic peripheral neuropathy, however an association was found between VEGF +405 genotypes and Indo-Asian which might have relevance to their lower rates of ulceration and amputation. This finding highlights the need for further investigation of any possible relationship between VEGF genotype, circulating VEGF concentrations and differential vulnerability to peripheral neuropathy amongst diabetic patients of different ethnic backgrounds.

Involvement of vascular endothelial growth factor (VEGF) gene polymorphism in hepatocellular carcinoma of HCV patients from local population

Development of Hepatocellular carcinoma (HCC) after Hepatitis C virus (HCV) infection is common cause of poor long-term survival. This study aimed to evaluate the effect of Vascular Endothelial growth factor (VEGF) genes polymorphism as a risk factor of Hepatocellular carcinoma (HCC) in chronic hepatitis C virus in Pakistani population. VEGF regulates angiogenesis so it is mainly involved in progression and development of solid tumor. The results showed that HCC patients had a higher frequency of the VEGF-634 GG genotype. In this study results revealed that VEGF Genotype GG is not associated with the risk of HCC in HCV infected patients in Punjab region of Pakistan. Keywords: HCV; HCC; VEGF Polymorphism http://dx.doi.org/10.19045/bspab.2017.60077

The VEGF gene polymorphism impacts brain volume and arterial blood volume.

Vascular endothelial growth factor (VEGF) plays a critical role in the angiogenesis and proliferation of various types of cells such as neurons, astroglia, and endothelial cells in the brain. A common polymorphism in the VEGF gene (-2578 C/A) is associated with circulating VEGF levels, cancers and Alzheimer's disease. Nonetheless, the effects of this polymorphism on normal human brain volume, arterial blood volume, and blood supply remain unclear. In this study, the effects of this polymorphism on the total gray matter volume (TGMV) and total white matter volume (TWMV) using T1-weighted structural images and the total arterial blood volume (TABV) and mean cerebral blood flow (mCBF) during rest using arterial spin labeling (ASL) in 765 young adult humans were investigated. Voxel-by-voxel whole-brain analyses of these measures were also performed. Multiple regression analyses with age and sex as covariates revealed that the VEGF genotype (number of C alleles) was significantly and positively correlated with TGMV, TWMV, and TABV as well as with regional gray and white matter volumes in widespread areas and regional arterial blood volume in some areas with high arterial blood volume. However, these regional associations were not seen when the corresponding global signal was included as a covariate in the multiple regression analyses, indicating that we failed to obtain evidence of region-specific associations between these brain measures and the genotype. The results suggest that the VEGF-2578C allele, is associated with changes in the vascular system that lead to increased blood volume and larger brain volume. Hum Brain Mapp 38:3516-3526, 2017. © 2017 Wiley Periodicals, Inc.

Clinical profile and role of VEGF-c polymorphism in prognosis and management of breast cancer

&lt;span class="Bold"&gt;Purpose:&lt;/span&gt;&lt;span&gt; Angiogenesis is a necessary step in tumor growth and metastasis. Vascular endothelial growth factor (VEGF-c) is a major mediator of breast cancer angiogenesis. Therefore, we investigated the association of polymorphism in the VEGF-c gene with breast cancer risk and prognostic characteristics of the tumors in a case-control study. &lt;/span&gt;&lt;span class="Bold"&gt;Experimental Design: &lt;/span&gt;&lt;span&gt;We examined one polymorphism in the VEGF-c gene (+936C/T) in 75 breast cancer cases and 75 control from Kanpur, Uttar Pradesh, India and adjacent areas together with geographically selected controls. &lt;/span&gt;&lt;span class="Bold"&gt;Results:&lt;/span&gt;&lt;span&gt; None of the polymorphism or any haplotype was significantly associated with either breast cancers. Our study suggests that the +936C/T polymorphism is unlikely to be associated with breast cancer. We also analyzed the cases for genotypes or haplotypes that associated with tumor characteristics. The genotypes and haplotypes were not related with other tumor characteristics such as regional or distant metastasis, stage at diagnosis, or dietary history. &lt;/span&gt;&lt;span class="Bold"&gt;Conclusions: &lt;/span&gt;&lt;span&gt;Although none of the polymorphisms studied in the VEGF-c gene was found to influence susceptibility to breast cancer significantly, some of the VEGF-c genotypes and haplotypes may influence tumor growth through an altered expression of VEGF-c and tumor angiogenesis.&lt;/span&gt;

Association between VEGF Gene Polymorphisms and In-Stent Restenosis after Coronary Intervention Treated with Bare Metal Stent.

Background. In-stent restenosis (ISR) is the gradual narrowing of the vessel lumen after coronary stent implantation due to the increase in vascular smooth muscle cell proliferation. Vascular endothelial growth factor (VEGF) protein plays an important role in this process. Our aim was to analyze the association of single nucleotide polymorphisms of the VEGF gene (rs2010963 and rs6999447) with the occurrence of ISR after coronary artery bare metal stent (BMS) implantation. Methods. 205 patients with a history of BMS implantation and a repeated coronarography were prospectively enrolled. Patients were assigned to diffuse restenosis group (n = 105) and control group (n = 100) and VEGF genotypes were determined. Results. Diffuse ISR was significantly more frequently observed in patients with homozygous normal genotype of rs2010963 polymorphism, and this polymorphism was independently associated with diffuse ISR. Conclusions. RS2010963 is associated with higher incidence of development of diffuse coronary ISR in patients treated with BMS implantation.

Combination of Angiotensin Converting Enzyme Insertion/Deletion (I/D) (rs4646994) and VEGF Polymorphism (+405G/C; rs2010963) Synergistically Associated With the Development, of Albuminuria in Iranian Patients With Type 2 Diabetes.

Background:Angiotensin-converting enzyme (ACE) insertion/deletion (I/D) and vascular endothelial growth factor (VEGF) polymorphisms have been shown to associate with diabetic nephropathy (DN).Objectives:We examined the hypothesis that ACE-D and VEGF-G alleles act synergistically in association with DN, in patients with type 2 diabetes mellitus (T2DM).Patients and Methods:The VEGF (rs2010963) and ACE (rs4646994) genotypes were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 490 T2DM patients. Diabetic patients were classified as T2DM patients with and without albuminuria (control). The PCR and RFLP were used to detect the VEGF and ACE alleles.Results:A total of 255 consecutive patients with T2DM and microalbuminuria (Group A) and 235 patients with T2DM and normoalbuminuria (Group B) were included in the study. In univariate analysis, the groups were statistically similar for all variables, except for glycated hemoglobin (HbA1c) (P = 0.034), and the frequency of ACE (P = 0.015) and VEGF (P = 0.006) genotypes. Our study showed that the VEGF-G and ACE-D alleles are independently associated with the development of nephropathy. According to our data, the combination of these two risk factors had a significant synergistic effect on the risk of microalbuminuria development.Conclusions:Our study indicated that ACE-D and VEGF-G alleles can be an independent risk factor for microalbominuria in T2DM patients.

Association of VEGF and VEGFR1 polymorphisms with breast cancer risk in North Indians.

The aim of present study was to evaluate the relationship between vascular endothelial growth factor (VEGF) -2578C/A, -2549I/D, -460T/C and -7C/T and VEGFR1 -710C/T polymorphisms with risk to breast cancer in North Indians. A total of 204 sporadic breast cancer patients and 204 controls were recruited for this case-control study. Significantly increased frequency of II genotype of -2549I/D polymorphism was observed in patients as compared to control individuals (odds ratio (OR) = 2.76, 95 % confidence interval (CI), 1.55-4.92; p = 0.0005). VEGF -2578AA genotype (OR = 2.87; 95 % CI, 1.61-5.10; p = 0.0003) and A allele (OR = 1.65, 95 % CI, 1.25-2.18; p = 0.0004) were found to be associated with increased risk for breast cancer. Individuals carrying CC genotype (OR = 2.23, 95 % CI, 1.25-3.97) and C allele (OR = 1.42, 95 % CI, 1.07-1.87) of VEGF -460T/C polymorphism were at higher risk of breast cancer. There was no significant difference in genotype and allele distribution of VEGF -7C/T and VEGFR1 -710C/T polymorphisms between cases and control individuals (p > 0.05). Linkage disequilibrium analysis showed a strong linkage between VEGF -2549I/D and -2578C/A polymorphisms (Lewontin's [Formula: see text] = 0.99; r (2) = 0.97), -2549I/D and -460T/C ([Formula: see text] = 0.94; r (2) = 0.84), and -2578C/A and -460T/C polymorphisms ([Formula: see text] = 0.93; r (2) = 0.83). In the present study, we concluded that VEGF -2549I/D, -2578C/A and -460T/C polymorphisms are associated with risk to breast cancer in Punjab, North India.