Vascular Endothelial Growth Factor Polymorphisms Research Articles

Evaluation of VEGF gene polymorphisms and proliferative diabetic retinopathy in Mexican population

To assess if the included vascular endothelial growth factor (VEGF) polymorphisms rs3025035, rs3025021 and rs2010963 are associated to proliferative retinopathy in a Mexican population with type 2 diabetes mellitus (T2DM). A case-control study was conducted in adult individuals with T2DM associated to proliferative retinopathy or non-proliferative retinopathy from Oct. 2014 to Jun. 2015 from the Retina Department of the Asociation to Prevent Blindness in Mexico. The selected patients were adults with a diagnosis of T2DM ≥5y. All subjects had a comprehensive ocular examination and the classification of the retinopathy severity was made considering the Early Treatment Diabetic Retinopathy Study (ETDRS) standardization protocols. Genomic DNA was extracted from whole fresh blood. All samples were genotyped by qPCR for selected VEGF polymorphisms. Hardy-Weinberg equilibrium was calculated by comparing Chi-square values between the expected and the observed values for genotype counts. In total 142 individuals were enrolled, 71 individuals with T2DM and associated proliferative retinopathy and 71 individuals with non-proliferative retinopathy. One-sided Fisher's exact test was performed for rs3025021 [OR (95% CI)=0.44(0.08-2.2); P=0.25] and rs2010963 [OR (95% CI)=0.63(0.25-1.6); P=0.23]. The minor allelic frequencies obtained were 26% for rs3025021, 10% for rs3025035 and 61% for rs2010963. The pairwise linkage disequilibrium between the three SNP was assessed, and was as follows: rs3025021 vs rs3025035: D'=1.0, r2=0.1043, P≤0.0001; rs3025021 vs rs2010963: D'=0.442, r2=0.0446, P=0.149; rs3025035 vs rs2010963: D'=0.505, r2=0.0214, P=0.142. This is the first analysis involving VEGF polymorphisms and proliferative diabetic retinopathy in a Mexican population. A major finding of the present study is that none of the polymorphisms studied was significantly associated with proliferative retinopathy. Based on these results, we can infer that different populations have different associations for the same polymorphisms.

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

<span class="Bold">Purpose:</span><span> 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. </span><span class="Bold">Experimental Design: </span><span>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. </span><span class="Bold">Results:</span><span> 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. </span><span class="Bold">Conclusions: </span><span>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.</span>

The Role of Vascular Endothelial Growth Factor Gene Polymorphisms in Recurrent Spontaneous Abortions in Saudi Women

Vascular endothelial growth factor (VEGF) genes regulate proliferation of vascular endothelial cells, hence, are essential for both physiological and pathological angiogenesis. The aim of the present study was to examine the association between three common VEGF single nucleotide polymorphisms (-583 T/C, -1154 G/A, and 936 C/T) and the risk of RSA in Saudi women. A total of 200 women; 100 with RSA-patient matched with 100 controls were enrolled sequentially. Genotyping was conducted using TaqMan assay in order to detect single nucleotide polymorphism (SNPs) in DNA extracts from blood samples. Results showed that the +936C/T allele of VEGF gene is not associated with increased risk of RSA. On the other hand, polymorphisms within -583T/C and -1154G/A of the promotor region were significantly associated with increased RSA risk. Based on these it can be concluded that polymorphisms of VEGF are associated with increased risk of RSA in Saudi women. Hence VEGF gene polymorphism can be a useful biomarker to predict susceptibility to RSA.

Prognostic significance of vascular endothelial growth factor polymorphisms in colorectal cancer patients.

AIMTo investigate the associations of the genetic polymorphisms of vascular endothelial growth factor A (VEGF-A) -1498C>T and -634G>C, with the survival of patients with colorectal cancer (CRC).METHODSA prospective cohort consisting of 131 Brazilians patients consecutively operated on with a curative intention as a result of sporadic colorectal carcinoma was studied. DNA was extracted from peripheral blood and its amplification and allelic discrimination for each genetic polymorphism was performed using the technique of polymerase chain reaction (PCR) in real-time. The real-time PCR technique was used to identify the VEGF-A -1498C>T (rs833031) and -634G>C (rs2010963) polymorphisms. Genotyping was validated for VEGF-A -1498C>T polymorphism in 129 patients and for VEGF-A -634G>C polymorphism in 118 patients. The analysis of association between categorical variables was performed using logistic regression, survival by Kaplan-Meier method and multivariate analysis by the Cox regression method.RESULTSIn the univariate analysis there was a significant association (OR = 0.32; P = 0.048) between genotype CC of the VEGF-A -1498C>T polymorphism and the presence of CRC liver metastasis. There was no association between VEGF-A -1498C>T polymorphism and VEGF-A -634G>C polymorphism with further clinical or anatomopathologic variables. The genotype CC of the VEGF-A -1498C>T polymorphism was significantly correlated with the 5-year survival (P = 0.032), but not significant difference (P = 0.27) was obtained with the VEGF-A -634G>C polymorphism with the 5-year survival in the univariate analysis. The genotype CT (HR = 2.79) and CC (HR = 4.67) of the polymorphism VEGF-A -1498C>T and the genotype CC (HR = 3.76) of the polymorphism VEGF-A -634C>G acted as an independent prognostic factor for the risk of death in CRC patients.CONCLUSIONThe CT and CC genotypes of the VEGF-A -1498C>T and the CC genotype of the VEGF-A -634C>G polymorphisms are prognostic factors of survival in Brazilians patients with sporadic colorectal carcinoma.

Vascular endothelial growth factor G+405C polymorphism may contribute to the risk of developing papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. Vascular endothelial growth factor (VEGF) is a mediator implicated with cell proliferation, differentiation and migration, and monocyte/macrophage chemotaxis. In present study, we aimed to investigate the relationship between VEGF gene polymorphisms (G+405C, T-460C, and A-2578C) and PTC susceptibility. DNA was isolated from peripheral blood leukocytes of 127 patients with PTC and 203 healthy controls. Genotyping was performed by real-time PCR. Association of genotypes with susceptibility of PTC was analyzed with multivariate logistic regression adjusted for age, gender and smoking status. In G+405C polymorphism, the frequencies of C allele (related with increased VEGF production) and combined CG+CC genotype were found to be higher (3.5 and 5-fold, respectively) among patients with PTC than controls (P<.001). However, VEGF T-460C and A-2578C polymorphisms are not associated with PTC risk. There was no relationship between VEGF polymorphisms and clinical/laboratory parameters of PTC. Haplotype analysis demonstrated that there was a strong linkage disequilibrium (LD) between -460/-2578 (D'=.89, r2 =.79), weak LD between +405/-460 (D'=.422, r2 =.035), and +405/-2578 (D'=.43, r2 =.038) locuses. Additionally, the +405/-460/-2578 GTA haplotype was found to be protective, whereas CTA haplotype to be related with increased PTC risk. As a conclusion, we suggest that VEGF G+405C polymorphism is associated with increased risk of PTC.

Correlation between circulating VEGF levels and disease activity in rheumatoid arthritis: ameta-analysis.

To systematically review evidence regarding the relationship between circulating vascular endothelial growth factor (VEGF) levels and rheumatoid arthritis (RA), the correlation between serum VEGF levels and RA activity, and the association between VEGF polymorphisms and RA susceptibility. We conducted ameta-analysis of the serum/plasma VEGF levels in patients with RA and controls, the correlation coefficients between the circulating VEGF levels and disease activity in patients with RA, and the association between VEGF -2578A/C, -634C/G, +936T/C, and -1154A/G polymorphisms and the risk for RA. In total, 13studies including 2508patients with RA and 2489controls were included. Meta-analysis revealed that VEGF level was significantly higher in the RA than in the control group (standard mean difference [SMD]= 1.480, 95% confidence interval [CI]= 0.71-2.241, p= 1.4× 10-4). Stratification by adjustment for age and gender revealed significantly higher VEGF levels for the adjustment and non-adjustment groups in the RA group (SMD= 1.360, 95% CI= 0.445-2.276, p= 0.004; SMD= 1.557, 95% CI= 0.252-2.861, p= 0.019, respectively). Meta-analysis of correlation coefficients showed asignificantly positive correlation between circulating VEGF levels and disease activity in RA, and between circulating VEGF and C‑reactive protein levels. However, no association was found between RA and the VEGF -2578A/C, -634C/G, +936T/C, and -1154A/G polymorphisms. Our meta-analysis revealed significantly higher circulating VEGF levels in patients with RA and apositive correlation between VEGF levels and disease activity in RA, but no association between the VEGF -2578A/C, -634C/G, +936T/C, and -1154A/G polymorphisms and the development of RA.

The GG genotype of the -152 G/A vascular endothelial growth factor (VEGF) polymorphism predisposes to hypertension-related chronic kidney disease.

Our purpose was to determine whether the VEGF -152 G/A polymorphism could be associated with chronic kidney disease and endothelial dysfunction in hypertensive patients. There were 100 healthy volunteers enrolled into the control group. The group of patients was constituted by 99 consecutively admitted hypertensive patients referred to our Institution by their general practitioner. All patients were treated with anti-hypertensive polytherapy. Presented study revealed that the hypertensive patients bearing the GG genotype were characterized by the highest values of diastolic blood pressure and markers of endothelial damage such as Angiogenin, Endostatin, CRP as well as von Willebrandt factor. In addition, higher number of immature endothelial progenitor cells with CD34(+)CD133(+), CD34(+)CD133(-) markers was observed in GG hypertensive carriers while in normotensive individuals no differences were found. Such phenomenon may indicate an increased mobilization of bone-marrow derived endothelial progenitors. It may testify to the preserved compensatory mechanism in chronic kidney disease (CKD) patients until the G3a stage of the disease. Moreover, patients with higher estimated glomerular filtration rate (eGFR) level had lower of vWf and Endostatin values, and higher level of VEGF. Taken together our findings clearly indicate the -152 GG hypertensive carriers as more prone to develop CKD. We can suspect that the VEGF -152 GG genotype is strongly associated with hypertension-dependent CKD.

Vascular endothelial growth factor polymorphism (–460 T/C) is related to hypertension-associated chronic kidney disease

ABSTRACTOur aim was to characterize the endothelial progenitor cells (EPCs) in normotensive controls and treated hypertensive individuals within the vascular endothelial growth factor (VEGF) –460 C/T polymorphism as well as to investigate whether this polymorphism predisposes to hypertension-related chronic kidney disease. The hypertensive patients bearing the TT genotype had the highest levels of immature EPC with the following phenotypes: CD34+, CD34+CD45dim, CD34+CD133+CD45dim. The study showed the estimated glomerular filtration rate values significantly lower and creatinine and BUN parameters higher among the TT hypertensive patients. We presume that the highest mobilization of EPCs from bone marrow may signalize more severe renal hypertension-related complications in the VEGF –460 TT genotype.

Vascular endothelial growth factor polymorphisms are associated with osteosarcoma susceptibility.

Polymorphisms in the vascular endothelial growth factor (VEGF) gene may contribute to osteosarcoma risk, but the results of previous studies have been inconsistent and inconclusive. We conducted a meta-analysis to assess this association more accurately. Relevant studies were collected systemically from three online English databases. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations of three VEGF gene polymorphisms (+936C/T, '634 G/C, +1612 G/A) with osteosarcoma risk. Seven case-control studies involving 1,350 cases and 1,706 controls were selected for the meta-analysis. The pooled OR indicated that the VEGF +936C/T polymorphism was associated with increased risk of osteosarcoma in a Chinese population (T vs. C: OR = 1.26, 95% CI = 1.12–1.42, P < 0.01; TT vs. CC: OR = 1.70, 95% CI = 1.29–2.24, P < 0.01; CT + TT vs. CC: OR = 1.23, 95% CI = 1.06–1.44, P < 0.01; TT vs. CC + CT: OR = 1.61, 95% CI = 1.23–2.10, P < 0.01). A significant association was also found between the −634 G/C polymorphism and osteosarcoma risk (C vs. G: OR = 0.81, 95% CI = 0.69-0.96, P = 0.01; CC vs. GG: OR = 0.66, 95% CI = 0.48–0.90, P < 0.01; GC + CC vs. GG: OR = 0.80, 95% CI = 0.67–0.96, P = 0.02; CC vs. GG + GC: OR = 0.72, 95% CI = 0.60–0.86, P < 0.01). In sum, our meta-analysis suggests VEGF polymorphisms are associated with osteosarcoma susceptibility in the Chinese population. However, further studies that include different ethnicities and larger populations are needed.

The associations of vascular endothelial growth factor gene polymorphisms with susceptibility to osteosarcoma: evidence from a meta-analysis.

Several studies have investigated the associations of the vascular endothelial growth factor (VEGF) gene polymorphisms with the susceptibility to osteosarcoma, while their conclusions are conflicting. This meta-analysis was performed to provide a comprehensive assessment on those associations. Electronic bibliographic databases were searched for potential studies focused on the relationship between VEGF polymorphisms and the susceptibility to osteosarcoma on 10 December 2015. Pooled odds ratios with 95% confidence intervals were conducted to assess the associations. After strict screening process, six articles consisted of 1220 osteosarcoma patients and 1576 controls were selected. The pooled results suggested that VEGF-2578C/A polymorphism was significantly associated with osteosarcoma risk in all genetic models as well as VEGF-634G/C polymorphism. When it came to VEGF+936C/T polymorphism, we detected significant associations under allele contrast, heterozygote, dominant and recessive models. As to VEFG-460T/C polymorphism, significant associations were demonstrated in allele contrast and heterozygote models. With regard to VEGF-1156G/A polymorphism, significant association was observed only in alleles contrast model. However, there was no significant association between VEGF-1612G/A polymorphism and risk of osteosarcoma. This meta-analysis suggests that these polymorphisms comprised of VEGF-2578C/A, VEGF-1156G/A, VEGF+936C/T, VEGF-634G/C and VEGF-460T/C are associated with osteosarcoma risk in Chinese Han population.

VEGF Gene Polymorphisms Affect Serum Protein Levels and Alter Disease Activity and Synovial Lesions in Rheumatoid Arthritis

BackgroundOur study investigated 2 common single-nucleotide polymorphisms (SNPs) of vascular endothelial growth factor (VEGF) for their influences on serum VEGF levels, disease activity, and synovial lesions in rheumatoid arthritis (RA).Material/MethodsClinical information and venous blood samples were collected from 98 RA patients and 100 healthy controls. Genotyping on samples from the subjects was performed using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). Serum VEGF levels were determined using the enzyme-linked immunosorbent assay (ELISA). The synovial thickness and joint effusion of 28 joints were measured in RA patients, and total sharp score (TSS) and disease activity score (DAS) of 28 joints were recorded.ResultsThe genotype and allele frequencies of VEGF rs833070 (G>A) and rs3025030 (G>C) were significantly different between RA group and control group (all P<0.05). VEGF rs833070 and rs3025030 polymorphisms were associated with increasing VEGF serum levels in the RA group (all P<0.01). Statistically significant difference was observed in DAS28 between the different genotypes of VEGF rs833070 in RA patients (P<0.05). Importantly, significant differences in synovial thickening, joint effusion and synovial angiogenesis were observed between the different genotypes of VEGF rs833070 and rs3025030 polymorphisms (all P<0.05).ConclusionsOur study provides evidence that VEGF polymorphisms might be important indicators of disease activity and synovial lesions, and prognostic factors in evaluating the treatment effectiveness in RA.

Association between Vascular Endothelial Growth Factor Polymorphisms and Age-Related Macular Degeneration: An Updated Meta-Analysis.

Age-related macular degeneration (AMD) is the most common cause of blindness in elderly people worldwide and the major degenerative disease of the retina that leads to progressive impairment of central vision. Several polymorphisms in different genes have been proposed as factors that increase the disease susceptibility. The aim of the present study is to carry out a systematic review and an updated meta-analysis in order to summarize the current published studies and to evaluate the associations between four common vascular endothelial growth factor (VEGF) polymorphisms (rs833061, rs1413711, rs3025039, and rs2010963) and AMD risk, also stratifying for AMD subtypes and ethnicity. A systematic literature search in the Medline database, using PubMed, was carried out for epidemiological studies, published before June 2016. Associations of VEGF polymorphisms with AMD were estimated by calculating pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) based on different models. Twelve articles were included in the analysis. The present meta-analysis constitutes a useful guide for readers to study AMD and adds new evidence to the growing literature on the role of VEGF polymorphisms in the risk of AMD. Significant associations with AMD risk were showed for rs833061, rs1413711, and rs3025039 polymorphisms but not for rs2010963.

The Different Effect of VEGF Polymorphisms on the Prognosis of Non-Small Cell Lung Cancer according to Tumor Histology.

Vascular endothelial growth factor (VEGF) contributes to tumor angiogenesis. The role of VEGF single nucleotide polymorphisms (SNPs) in lung cancer susceptibility and its prognosis remains inconclusive and controversial. This study was performed to investigate whether VEGF polymorphisms affect survival outcomes of patients with early stage non-small cell lung cancer (NSCLC) after surgery. Three potentially functional VEGF SNPs (rs833061T>C, rs2010963G>C, and rs3025039C>T) were genotyped. A total of 782 NSCLC patients who were treated with surgical resection were enrolled. The association of the SNPs with overall survival (OS) and disease free survival (DFS) was analyzed. In overall population, none of the three polymorphisms were significantly associated with OS or DFS. However, when the patients were stratified by tumor histology, squamous cell carcinoma (SCC) and adenocarcinoma (AC) had significantly different OS (Adjusted hazard ratio [aHR] = 0.76, 95% CI = 0.56–1.03 in SCC; aHR = 1.33, 95% CI = 0.98–1.82 in AC; P for heterogeneity = 0.01) and DFS (aHR = 0.75, 95% CI = 0.58–0.97 in SCC; aHR = 1.26, 95% CI = 1.00–1.60 in AC; P for heterogeneity = 0.004) according to the rs833061T>C genotypes. Our results suggest that the prognostic role of VEGF rs833061T>C may differ depending on tumor histology.

VEGF Polymorphisms Related to Higher Serum Levels of Protein Identify Patients with Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary neoplasia of the liver. Major risk factors for hepatocellular carcinoma include chronic liver diseases, carcinogenic agents, and genetic alterations as well as vascular endothelial growth factor (VEGF) involved in angiogenesis process. The aim of this study was to evaluate the association of VEGF-A (C936T and A1154G) with HCC and cirrhosis, in addition to serum levels of VEGF, clinical profile, lifestyle habits, and comorbidities. A total of 346 individuals were studied: 102 with HCC (G1), 117 with cirrhosis (G2), and 127 controls (G3). Polymorphisms were analysed by PCR/RFLP and serum levels of VEGF by ELISA. Alpha error was set at 5%. The wild-type genotype of both polymorphisms prevailed (P > 0.05). In G1, 23% of the patients died, with no relation to genetic profile (P > 0.05). Increased VEGF level was observed in G1 and G3, related to the mutant allele of VEGF-C936T and VEGF-A1154G, respectively, and compared with the wild-type genotype (P = 0.0285; P = 0.0284, resp.) as well as G1 versus G2 and G3 for VEGF-C936T and G1 versus G2 for VEGF-A1154G (P < 0.05 for both). In conclusion, there is a relationship between mutant alleles of VEGF-C936T and VEGF-A1154G polymorphisms and higher VEGF level, making them potential markers for HCC.

Vascular Endothelial Growth Factor Gene Polymorphism (rs2010963) and Its Receptor, Kinase Insert Domain-Containing Receptor Gene Polymorphism (rs2071559), and Markers of Carotid Atherosclerosis in Patients with Type 2 Diabetes Mellitus.

Background. The current study was designed to reveal possible associations between the polymorphisms of the vascular endothelial growth factor (VEGF) gene (rs2010963) and its receptor, kinase insert domain-containing receptor (KDR) gene polymorphism (rs2071559), and markers of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Patients and Methods. 595 T2DM subjects and 200 control subjects were enrolled. The carotid intima-media thickness (CIMT) and plaque characteristics (presence and structure) were assessed ultrasonographically. Biochemical analyses were performed using standard biochemical methods. Genotyping of VEGF/KDR polymorphisms (rs2010963, rs2071559) was performed using KASPar assays. Results. Genotype distributions and allele frequencies of the VEGF/KDR polymorphisms (rs2010963, rs2071559) were not statistically significantly different between diabetic patients and controls. In our study, we demonstrated an association between the rs2071559 of KDR and either CIMT or the sum of plaque thickness in subjects with T2DM. We did not, however, demonstrate any association between the tested polymorphism of VEGF (rs2010963) and either CIMT, the sum of plaque thickness, the number of involved segments, hsCRP, the presence of carotid plaques, or the presence of unstable carotid plaques. Conclusions. In the present study, we demonstrated minor effect of the rs2071559 of KDR on markers of carotid atherosclerosis in subjects with T2DM.

Genetic variants of vascular endothelial growth factor are associated with recurrent implantation failure in Korean women

Vascular endothelial growth factor (VEGF) is involved in embryonic development, decidual vascularization and placenta angiogenesis. This study was performed to determine whether there is an association between genetic polymorphisms in the VEGF gene and the development of recurrent implantation failure (RIF) in Korean women. A total of 119 women diagnosed with RIF and 236 control subjects were genotyped for VEGF polymorphic sites including rs833061 (-460T>C), rs25648 (-7C>T) and rs3025020 (-583C>T) using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays and real-time PCR. The VEGF rs833061 C allele and rs25648 T allele were significantly associated with increased RIF risk (odds ratio [OR] = 1.813 [1.161–2.831], P = 0.009, OR = 2.213 [1.254–3.903], P = 0.005). The rs833061/rs25648 TC/CT, TC/CT+TT, and rs833061/rs3025020 TC+CC/TT genotypes were more frequent in the RIF group compared with the control group (OR = 2.130 [1.092–4.156], P = 0.025, OR = 2.130 [1.092–4.156], OR = 4.261 [1.163–15.620], P = 0.028, respectively). The results of this study suggests that VEGF polymorphisms are associated with RIF development. Therefore, we postulate that VEGF polymorphisms might be useful markers to predict RIF development. Further studies are warranted to elucidate the role of VEGF variants and RIF development.

Vascular endothelial growth factor (VEGF)-634G/C polymorphism was associated with severe pre-eclampsia and lower serum VEGF level.

Vascular endothelial growth factor (VEGF) is an angiogenic factor whose production is increased in pre-eclampsia (PE). Therefore, the present study was conducted aiming at assessing the possible association of VEGF polymorphisms with PE susceptibility in the southeast of Iran. Overall, 192 PE women and 186 unrelated age-matched normotensive pregnant women were genotyped for the VEGF-2578C/A (rs699947), -1154G/A (rs1570360), and -634G/C (rs2010963) polymorphisms using the polymerase chain reaction-restriction fragment length polymorphism method. Serum VEGF levels were determined by the enzyme-linked immunosorbent assay method. There was no significant difference in VEGF-2578C/A, -1154G/A and -634G/C polymorphisms between PE women and controls. However, the frequency of VEGF-634GC and CC genotypes was significantly higher in women with severe PE compared to mild PE and controls. In addition, serum VEGF levels were significantly lower in PE women. The VEGF-634CC genotype was associated with lower serum VEGF levels compared to the VEGF-634GG genotype. Moreover, serum VEGF levels were significantly lower in individuals with the VEGF-634CC genotype compared to VEGF-634GC genotype only in the control group. The mean serum VEGF levels did not differ significantly between genotypes of VEGF-2587C/A and -1154G/A polymorphisms. Our findings suggest that the association of VEGF-634G/C polymorphisms with severe PE and the VEGF-634CC genotype was correlated with lower serum VEGF levels.

ROLE OF VASCULAR ENDOTHELIAL GROWTH FACTOR IN NON-SMALL CELL LUNG CANCER PATHOGENESIS

The angiogenesis is an important process in the pathogenesis of malignancies. It is regulated by various growth factors, with the vascular endothelial growth factor (VEGF) playing the central role. The aim of the present study was to evaluate possible associations of functional VEGF -2578C>A, -634G>C, and +936C>T polymorphisms with the risk for occurrence and progression of non-small cell lung cancer (NSCLC) in patients living in Republic of Belarus. A total of 202 patients (147 males and 55 females) diagnosed as having the NSCLC. The control group consisted of 336 individuals (245 males and 91 females) without an oncopathology. The total DNA was isolated from peripheral blood. We investigated the single nucleotide polymorphisms of VEGF (rs 2010963), (rs 699947), (rs 3025039). The genotyping was performed by PCR-RFLP analysis. Our results revealed a marginally significant association of the -2578CC genotype (p=0.002) with a greater degree of tumor spread (Т2-Т4). Heterozygous genotypes -2578СА and +936СT carriers were included into the follow-up group significantly more often (р=0.021 and р=0.012, respectively). Our study demonstrate that VEGF -2578A/C and +936C/T polymorphisms are among the factors determining the individual peculiarities of NSCLC course in this population and can be used for clarifying the prognosis of the disease.

Vascular endothelial growth factor polymorphisms and a synchronized examination of plasma and tissue expression in epithelial ovarian cancers.

In this study, we have analyzed six genetic polymorphisms of the VEGF-A gene and correlated the genetic data with plasma and tissue expression of VEGF-A in epithelial ovarian carcinomas. A total of 130 cases including 95 malignant carcinomas, 17 low malignant potential and 18 benign tumours were studied. rs699947, rs833061, rs1570360, rs2010963, rs1413711 and rs3025039 were studied by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Plasma levels of VEGF-A were estimated by enzyme-linked immunosorbent assay (ELISA) and tissue expression of VEGF-A by immunohistochemistry (IHC). Four polymorphisms of the above excluding rs699947 and rs3025039 showed significant association with malignancy, and we observed the presence of positive correlation between haplotype CCGGCC and increased expression of VEGF-A in both plasma and tissues which also correlated with poor prognosis and recurrence suggesting a probable increase in resistance to treatment in such carriers. Highly upregulated tissue expression of VEGF-A was seen in all epithelial ovarian carcinomas with intensity of expression increasing from benign to malignant cases. ELISA data from our study showed an increase in circulating levels of VEGF-A in malignancies. VEGF-A plasma levels can be employed as a biomarker for high-grade malignancy in epithelial ovarian cancers alongside tissue expression and CA-125 levels. This study is unique due to the fact that a simultaneous analysis of plasma and tissue expression has been demonstrated and is a first such study in epithelial ovarian cancers and representing the Indian population (South-east Asian) synchronized with genetic polymorphism data as well.

Genetic association between VEGF polymorphisms and BRONJ in the Korean population.

The purpose of this study was to evaluate the association between vascular endothelial growth factor (VEGF) polymorphisms and bisphosphonate-related osteonecrosis of the jaw (BRONJ) in the Korean population. Forty-five individuals (2 men, 43 women; mean age: 68.7 ± 12.3 years) were recruited for this study. All visited the Yonsei University Dental Hospital for surgical intervention from January 2012 to January 2013 and had a history of bisphosphonate (BP) administration (oral and/or intravenous). Patients were allocated to case (n = 26) or control (n = 19) groups according to the patients' selection criteria. Association between three VEGF single nucleotide polymorphisms (rs699947 (-2578 C>A), rs2010963 (-634 G>C) and rs3025039 (+936 C>T)) and BRONJ were investigated using multiple logistic regression analysis and Fisher's exact test where appropriate (α = 0.05). The CC homozygotes of rs2010963 and rs3025039 of VEGF gene were associated with an increased risk of BRONJ (P = 0.04, 0.03, respectively). In haplotype analysis, no differences in haplotype C-C (-2578/-634) and haplotype C-C-C (-2578/-634/+936) were observed. The CC homozygotes of rs2010963 and rs3025039 polymorphisms in the VEGF gene were associated with an increased risk of BRONJ in the Korean population. Further epidemiological cohort studies with a larger sample size would be required to confirm the suggestive correlations.