Vascular Endothelial Growth Factor Rs2010963 Research Articles

VEGF genetic polymorphisms may contribute to the risk of diabetic nephropathy in patients with diabetes mellitus: a meta-analysis.

Objective. This meta-analysis aimed to investigate a comprehensive and reliable conclusion on the correlations of single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor (VEGF) gene with the risk of diabetic nephropathy (DN) in patients with diabetes mellitus (DM). Methods. We screened PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, CBM, and CNKI databases for those relevant studies that investigated the association of 14,945 subjects with clinicopathological parameters in gastric cancer. Results. Eleven case-control studies that met all inclusion criteria were included in this meta-analysis. A total of 14,945 subjects were involved, including 3,049 DN patients and 11,896 DM patients. Our meta-analysis results revealed that VEGF rs2010963 and rs3025039 polymorphisms might contribute to the risk of DN in DM patients. Ethnicity-stratified analysis suggested that VEGF genetic polymorphisms were associated with an increased risk of DN among Asians. However, we found no correlations of VEGF genetic polymorphisms with susceptibility to DN among Caucasians. Conclusion. Our findings suggest that VEGF rs2010963 and rs3025039 polymorphisms may contribute to the risk of DN in DM patients, especially among Asians. Thus, VEGF genetic polymorphisms could be useful biomarkers for early diagnosis of DN in DM patients.

The IL-8, VEGF, and CFH Polymorphisms and Bevacizumab in Age-related Macular Degeneration

Patients with exudative age-related macular degeneration (AMD) treated with vascular endothelial growth factor (VEGF) inhibitors require continuous follow-up and frequent reinjections. Finding predictors of the treatment response may assist in developing new treatment strategies. Previously we found an association between interleukin (IL)-8 rs4073 single nucleotide polymorphism and the initial anatomic response to bevacizumab in exudative AMD patients.1 To further explore the effects of genetic factors on the bevacizumab treatment outcome we analyzed in a prospective setting the associations of IL-8 rs4073 A→T, VEGF rs699947 A→C, rs2146323 A→C, and rs3025033 A→G, complement factor H (CFH) rs1061170 T→C, LOC387715 rs10490924 G→T, and complement component 3 rs2230199 C→G single nucleotide polymorphisms with the treatment response during 2 years of follow-up.

Angiotensin converting enzyme insertion/deletion (I/D) (rs4646994) and Vegf polymorphism (+405G/C; rs2010963) in type II diabetic patients: Association with the risk of coronary artery disease

Little is known about the concomitant presence of the angiotensin-converting enzyme (ACE) (rs4646994) D allele and vascular endothelial growth factor(VEGF) (+405G/C; rs2010963) G allele on the susceptibility of coronary artery disease (CAD). Here we examined the hypothesis that ACE-D and VEGF-G alleles act synergistically to increase the severity of CAD in patients with type II diabetes mellitus (T2DM). The VEGF (rs2010963) and ACE (rs4646994) genotypes were detected by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) and PCR, respectively in 510 T2DM patients undergoing their first coronary angiography. Diabetic patients were classified as T2DM patients with and without CAD (control). The crude odds ratio (OR) for the presence of CAD in ID+DD and D allele carriers were 1.98 (p=0.01) and 1.55 (p=0.001), respectively. Also, adjusted ORs in the presence of normolipidemia and the absence of history of hypertension for the risk of CAD in the either ACE(rs4646994) D allele or VGEF(rs2010963)-G alleles were 2.08 (p=0.004) and 1.75 (p=0.024), respectively. In addition, the concomitant presence of the ACE-D and VEGF-G alleles increased the risk of CAD 2.25-fold (p=0.043). Our results indicated that ACE(rs4646994)-D allele alone and in the presence of VEGF(rs2010963)-G allele can be an important independent risk factor for susceptibility of CAD in T2DM patients even after correcting for conventional risk factors in a population of Iran.

Assessment of the associations between three VEGF polymorphisms and risk of prostate cancer

Vascular endothelial growth factor (VEGF) plays a crucial role in the regulation of angiogenesis and is involved in the development and metastasis of common cancers. There were several case-controls studies published to assess the associations of VEGF polymorphisms with risk of prostate cancer, but the findings were inconsistent. We performed a meta-analysis to provide a comprehensive assessment of the associations of three VEGF polymorphisms with risk of prostate cancer. The pooled odds ratio (OR) with 95% confidence interval (95% CI) was calculated to assess the associations. Eleven individual case-control studies with a total of 5,209 cases of prostate cancer and 5,233 controls were finally included into our meta-analysis. Overall, VEGF rs833061 polymorphism was not associated with risk of prostate cancer (T versus C, OR = 1.14, 95% CI 0.91-1.44, P = 0.26; TT versus CC, OR = 1.09, 95% CI 0.67-1.76, P = 0.74; TT versus OR = 1.46, 95% CI 0.67-3.18, P = 0.34; TT/CT versus CC, OR = 1.08, 95% CI 0.82-1.43, P = 0.59). VEGF rs3025039 polymorphism was also not associated with risk of prostate cancer (T versus C, OR = 1.03, 95% CI 0.91-1.16, P = 0.66; TT versus CC, OR = 1.82 95% CI 0.16-20.53, P = 0.63; TT versus CC/CT, OR = 2.00, 95% CI 0.18-22.41, P = 0.57; TT/CT versus CC, OR = 0.72, 95% CI 0.38-1.36, P = 0.31). VEGF rs2010963 polymorphism was not associated with risk of prostate cancer under three models (C versus G, OR = 1.17, 95% CI 0.92-1.48, P = 0.20; CC versus GG, OR = 2.28, 95% CI 0.90-5.75, P = 0.08; CC versus GG/GC, OR = 1.57, 95% CI 0.67-3.68, P = 0.30). In conclusison, current data suggest that those three VEGF polymorphisms are not obviously associated with risk of prostate cancer.

VEGF A (rs699947 and rs833061) and VEGFR2 (rs2071559) Gene Polymorphisms are not Associated with AMD Susceptibility in a Spanish Population

Purpose: Age-related macular degeneration (AMD) is a multifactorial disease due to interaction between genetic and environmental factors. Increased angiogenesis plays a central role in AMD development. Previous studies on the potential link between AMD and vascular endothelial growth factor (VEGFA) and vascular endothelial growth factor receptor (VEGFR) have yielded conflicting results. We have analysed if polymorphisms in genes coding for VEGFA and VEGFR are associated to susceptibility to suffer AMD in a cohort of Spanish subjects.Patients and Methods: We obtained peripheral blood samples from 151 patients with diagnosis of exudative AMD. We also studied 91 healthy subjects matched by age. We studied VEGFA rs699947 and rs833061, and VEGFR2 rs2071559 polymorphisms using real-time PCR with TaqMan probes.Results: We did not find statistically significant differences in genotypic distribution of VEGF rs699947 and rs833061 polymorphisms between patients and controls. However, analysis of VEGFR2 rs2071559 polymorphism shows that carriers of GG genotype are more frequent in subjects with AMD (p: 0.032; Odds Ratio(OR): 1.933; confidence interval (CI): 1.053–3.549), but, when corrected by Bonferroni testing, the result was found to be not significant.Conclusion: Our study shows that VEGFA rs699947 and rs833061 and VEGFR2 rs2071559 polymorphisms do not modify the risk of suffering AMD in a Spanish population.

VEGFA, FLT1, KDR and colorectal cancer: Assessment of disease risk, tumor molecular phenotype, and survival

Angiogenesis is essential for tumor progression. Vascular endothelial growth factor (VEGFA) and its receptors 1 (FLT1) and 2 (KDR), have been identified as major mediators of this process. We hypothesized that genetic variation in FLT1 (38 SNPs), KDR (22 SNPS), and VEGFA (11 SNPs) would be associated with colon and rectal cancer development and survival. Data from a case-control study of 1555 colon cancer cases and 1956 controls and 754 rectal cancer cases and 959 controls were used. An adaptive rank truncation product (ARTP), based on 10,000 permutations, was used to determine the statistical significance of the candidate genes and angiogenesis pathway. Based on ARTP results, FLT1 was significantly associated with risk of colon cancer (P(ARTP) = 0.045) and VEGFA was significantly associated with rectal cancer (P(ARTP) = 0.036). After stratifying by tumor molecular subtype, SNP associations observed for colon cancer were: VEGFA rs2010963 with CIMP+ colon tumors; FLT1 rs4771249 and rs7987649 with TP53; FLT1 rs3751397, rs7337610, rs7987649, and rs9513008 and KDR rs10020464, rs11941492, and rs12498529 with MSI+ and CIMP+/KRAS2-mutated tumors. FLT1 rs2296189 and rs600640 were associated with CIMP+ rectal tumors and FLT1 rs7983774 was associated with TP53-mutated rectal tumors. Four SNPs in FLT1 were associated with colon cancer survival while three SNPs in KDR were associated with survival after diagnosis with rectal cancer. Aspirin/NSAID use, smoking cigarettes, and BMI modified the associations. These findings suggest the importance of inflammation and angiogenesis in the etiology of colorectal cancer and that genetic and lifestyle factors may be targets for modulating disease risk.

Genetic factors regulating inflammation and DNA methylation associated with prostate cancer

Prostate cancer (PCa) displays a strong familiarity component and genetic factors; genes regulating inflammation may have a pivotal role in the disease. Epigenetic changes control chromosomal integrity, gene functions and ultimately carcinogenesis. The enzyme glycine-N-methyltransferase (GNMT) contributes to S-adenosylmethionine level regulation and, by affecting DNA methylation, influences gene expression. The genotype and allele distribution of single-nucleotide polymorphisms (SNPs) in the promoter regions of vascular endothelial growth factor (VEGF), interleukin (IL)-10, IL-1β, alpha-1-antichymotrypsin (ACT) and GNMT genes, the level of global DNA methylation and the influence of GNMT SNP upon DNA methylation in a PCa case-control study have been investigated. SNPs of VEGF (rs699947), ACT (rs1884082), IL-1β (rs16944), IL-10 (rs1800896) and GNMT (rs9462856) genes were assessed by PCR or by real-time PCR methods. DNA methylation was assessed by an ELISA assay. Frequencies of the VEGF AA genotype, the IL-10 A allele and GNMT T allele were higher in PCa. The concomitant presence of the AA genotype of VEGF, the A allele of IL-10 and T allele of GNMT increased the risk of PCa. Total DNA methylation was decreased in PCa; control GNMT T carriers (T+) showed the highest level of DNA methylation. SNPs in VEGF, IL-10 and GNMT genes might have a synergistic role in the development of PCa. The GNMT T allele may influence PCa risk by affecting DNA methylation and prostate gene expression. Our observations might help implement the screening of unaffected subjects with an increased susceptibility to develop PCa.

Role of Vascular Endothelial Growth Factor Polymorphisms in the Treatment Success in Patients with Wet Age-related Macular Degeneration

Along with environmental risk factors such as smoking, hypertension, and atherosclerosis, genetic susceptibility is a primary contributor to the development and progression of exudative age-related macular degeneration (AMD). Vascular endothelial growth factor (VEGF) is a central angiogenic regulator and there has been general agreement now that it is an important trigger for the progression of exudative AMD. In the present study, we tested the hypothesis that VEGF gene polymorphisms play a role in the treatment success with VEGF inhibitors in patients with exudative AMD. Prospective cohort study. We included 185 eyes of 141 patients with exudative AMD who were scheduled for their first treatment with intravitreally administered bevacizumab in this trial. All patients were aged >50 years and had angiographically verified exudative AMD. Blood from the finger pad was collected on blood cards for genotyping for the VEGF polymorphisms rs1413711, rs3025039, rs2010963, rs833061, rs699947, rs3024997, and rs1005230. At each follow-up visit, visual acuity was reassessed and an ophthalmic examination was carried out. Visual acuity outcome, number of retreatments, and overall time of treatment were analyzed in dependence of the VEGF polymorphisms. Mean change in visual acuity at the end of the treatment period. The included patients were reinjected with bevacizumab 1 to 15 times, resulting in a total treatment period of 42 to 1182 days. In univariate analysis only the G/G genotypes of rs3024997 and rs2010963 compared with all other 5 single nucleotide polymorphisms (SNPs) showed a significantly lower visual acuity at the end of treatment. In multivariate analysis including parameters such as time, baseline visual acuity, and number of reinjections, none of the SNPs showed a significant correlation. The current study indicates that VEGF polymorphisms are not major predictors of anti-VEGF treatment success in patients with exudative AMD.

Does VEGF polymorphism play a role in the treatment success with VEGF inhibitors in patients with CNV?

Abstract Purpose Along with risk factors like smoking, hypertension, atherosclerosis, and low choroidal blood flow, genetic susceptibility is a primary contributor to the development and progression of wet age‐related macular degeneration (AMD). Vascular endothelial growth factor (VEGF) is a central angiogenic regulator and there is general agreement now that it is one of the most important triggers for the progression of neovascular AMD. In the present study we tested the hypothesis that VEGF gene polymorphisms play a role in the treatment success with VEGF inhibitors in patients with CNV. Methods One‐hundred‐sixty‐two eyes of 143 patients with neovascular AMD who were scheduled for their first treatment with intravitreally administered ranibizumab were included in this trial. All patients were aged over 50 years and had angiographically verified neovascular AMD. Blood from the finger pad was collected on blood cards for genotyping for the VEGF polymorphisms rs1413711, rs3025039, rs2010963, rs833061, rs699947, rs3024997 and rs1005230. At each follow up visit, visual acuity was reassessed and an ophthalmic examination was carried out. The number of retreatments as well as the visual acuity outcome was analyzed in dependence of the VEGF polymorphisms. Results The included patients were reinjected with ranibizumab 2 to 19 times, resulting in a total treatment period of 42 to 1182 days. Neither the number of retreatments nor the visual acuity outcome was associated with any of the studied haplotypes. Conclusion The success of anti VEGF treatment is not dependent on VEGF gene polymorphisms.

Association of single nucleotide polymorphisms (SNPs) of VEGF gene with diabetic retinopathy

Abstract Purpose: Vascular endothelial growth factor (VEGF) has an important role in the development of diabetic retinopathy. High concentration of vitreous VEGF and elevated VEGF expression has been found in diabetic retinopathy. Single nucleotide polymorphisms (SNPs) of VEGF gene have been shown to influence expression of VEGF. We studied the association of VEGF SNPs with severity of diabetic retinopathy. Methods: The study population consisted of 129 diabetic (type 1 or type 2) patients with laser‐treated retinopathy, 99 diabetic patients with mild or no retinopathy and 524 non‐diabetic controls. SNPs were chosen on structural basis at three different haploblocks of the VEGF gene covering the whole VEGF gene and in addition, polymorphisms previously known to affect VEGF production were selected. VEGF SNPs rs699947, rs2010963, rs2146323, rs3025033 and rs3025039 were genotyped using the 5' nuclease assay for allelic discrimination (TaqMan). The allele and genotype frequencies were analyzed with chi‐square test in SPSS. Results: Duration of diabetes was similar in patients with laser‐treated retinopathy and in patients with mild or no retinopathy (mean 22.8 vs. 22.7 years, respectively), but the laser‐treated diabetic group had somewhat poorer glycemic control (9.2 vs. 8.4 %). The distribution of genotypes and the allele frequencies did not differ significantly between the diabetics and controls, between patients with laser‐treated retinopathy and patients with mild or no retinopathy, or between patients with proliferative retinopathy and patients with non‐proliferative retinopathy. Conclusions: In conclusion, these findings suggest that VEGF gene SNPs studied are not associated with the severity of diabetic retinopathy.