Vascular Endothelial Growth Factor Polymorphisms Research Articles

Vascular endothelial growth factor gene is associated with hypertensive cerebellar hemorrhage and rehabilitative treatment.

Early rehabilitative therapy is important for patients with hypertensive cerebral hemorrhage to improve long-term function of the extremities. Vascular endothelial growth factor (VEGF) is closely associated with the pathogenesis of hypertension. To identify the markers contributing to the genetic susceptibility to hypertensive cerebellar hemorrhage (HCH) and rehabilitative treatment, we examined the potential association between HCH and 12 single nucleotide polymorphisms of the VEGF gene. Participants included 244 patients with HCH and 251 healthy controls from our rehabilitation department. The T allelic frequencies of the rs3025020 (intron 6) and rs3025039 (3'-UTR) polymorphisms were significantly higher in the patients with HCH than in the healthy controls (rs3025020 T allele: P = 0.0002, OR = 1.619, 95%CI = 1.256-2.088; rs3025039 T allele: P = 0.001, OR = 1.682, 95%CI = 1.246-2.270). Strong linkage disequilibrium was observed in three blocks (D' > 0.9), and significantly more C-G-C (rs3025020, rs3025030, and rs3025039) haplotypes (P = 0.001) were found in the controls in block 3. Significantly more T-G-C haplotypes were found in the patients with HCH (P = 0.046). Further genotype and clinical phenotype correlation study of the rs3025039 carriers showed that Fugl-Meyer and Barthel index scores were lower in the patients with the TT genotype relative to CT + CC genotypes (P < 0.01). These findings point to a role for VEGF polymorphism in HCH, and may be informative for future investigations on the pathogenesis of rehabilitative treatment.

Vascular Endothelial Growth Factor: An Overview Across Multiple Disease Conditions

Vascular Endothelial Growth Factor (VEGF) is the major player in the regulation of physiological angiogenesis as well as it has also been implicated in pathological angiogenesis, associated with cancers and other conditions, among which psoriasis, autoimmune diseases and visual loss in macular degeneration. Interestingly, three regulatory Single Nucleotide Polymorphisms (rSNPs) in the promoter region of VEGF-A gene have been significantly associated with different human diseases and it is possible that, in the near future, the cumulative effect of several high-risk Single Nucleotide Polymorphisms (SNPs) may prove useful in a clinical setting. Currently, new VEGF inhibitors are undergoing clinical testing in various disease conditions, given that VEGF inhibition has also been contemplated as a possible strategy for prevention of angiogenesis and vascular leakage to decrease inflammation. This review focuses mainly on the role of Vascular Endothelial Growth Factor in several pathological contexts, highlighting the emerging association of the most common VEGF polymorphisms with disease risk. An update on the therapeutic implications of VEGF has also been documented.

Relationship of common vascular endothelial growth factor polymorphisms and haplotypes with the risk of cervical cancer in Tunisians

ObjectiveWe investigated the association between common vascular endothelial growth factor (VEGF) single nucleotide polymorphisms (SNPs) and the risk of cervical cancer (CC) in Tunisian patients and control women. MethodsStudy subjects comprised 86 CC cases and 124 control women. Genotyping of VEGF rs699947, rs833061, rs1570360, rs2010963, rs25648, rs833068, rs833070, rs3025039 SNPs was done by real-time PCR. ResultsHigher minor allele frequencies (MAF) of rs699947 (−2578C/A) [P=0.04; OR (95% CI)=1.52 (1.02–2.29)], and rs1570360 (−1154G/A) [P=0.04; OR (95% CI)=1.58 (1.01–2.47)] were seen in CC cases compared to control women. Marked differences in the distribution of rs699947 (P=9×10−4) and rs1570360 (P=0.03) genotypes were seen between CC cases and control groups; the distribution of the remaining SNPs was comparable between CC cases and control women. The association of rs699947 and rs1570360 with heightened CC risk with was seen in the heterozygous, and more so in the homozygous states. Haploview analysis revealed high LD between rs699947, rs833061, rs1570360, rs2010963, rs25648, rs833068 and rs833070 but weak or no LD between rs3025039 and the other SNPs. Seven-locus (rs699947/rs833061/rs1570360/rs2010963/rs25648/rs833068/ rs833070) haploview analysis identified only CTGCCAG haplotype to be positively associated with CC [P=0.022; OR(95% CI)=1.74 (1.08–2.79)]. ConclusionSpecific VEGF variants (rs699947, rs1570360) and haplotype (CTGCCAG) may contribute to the development of CC among Tunisian women.

Predictive value of vascular endothelial growth factor polymorphisms on the clinical outcome of renal cell carcinoma patients.

A cohort study was conducted to investigate the association between vascular endothelial growth factor (VEGF) polymorphisms −2578C/A, −1154G/A and −634C/G and the clinical outcome of renal cell carcinoma (RCC), as well as the interaction of VEGF polymorphisms with tumor stage, metastasis and size. A total of 310 RCC patients were recruited from the First Affiliated Hospital of Zhengzhou University (Zhengzhou, China) between January 2006 and December 2007, and were followed up until December 2012. The association between the three single nucleotide polymorphisms and the overall survival of RCC patients was estimated using Cox’s proportional hazard regression model. The median follow-up duration was 34.7 months and 74 of the RCC patients succumbed due to cancer during the follow-up period. The frequency of the VEGF −2578 AA genotype was significantly higher in patients classed as tumor stages III–IV (odds ratio [OR], 0.47; 95% confidence interval [CI], 0.24–0.95) and larger tumors (longest diameter, >4 cm; OR, 0.44; 95% CI, 0.22–0.89). Furthermore, the frequency of VEGF −634 GG was significantly higher in patients with larger tumors (longest diameter, >4 cm; OR, 0.68; 95% CI, 0.48–0.97). The VEGF −2578 AA genotype was correlated with a 2.96-fold increase in the risk of RCC-associated mortality and was associated with a five-year survival rate of ~25%. Therefore, the present study identified that the VEGF −2578C/A polymorphism may be associated with the prognosis of RCC patients, and may interact with the tumor stage and size.

Association study of vascular endothelial growth factor gene polymorphisms with ectopic pregnancy in Chinese women

Objective: The purpose of this study is to evaluate potential associations between vascular endothelial growth factor (VEGF) gene polymorphisms and ectopic pregnancy (EP) in Chinese women. Materials and Methods: This was a case–control study wherein 192 women with a history of EP were compared to 210 post-menopausal controls with two pregnancies and no EP for the genotyping of VEGF polymorphisms. Genotyping of the VEGF gene polymorphisms at -460C/T, -1154G/A, -2578C/A and +936C/T were performed by polymerase chain reaction-restriction fragment length polymorphism. Results: No significant differences were found in genotype and allele distributions of the -460C/T, +936C/T polymorphisms between cases and controls. Compared with the -1154G/G genotype, the -1154(A/A+G/A) genotype could significantly reduce the risk of developing EP. For the -2578C/A polymorphism, the A/A+C/A genotype could significantly decrease the risk of developing EP, compared with the C/C genotype. The haplotype analysis suggested that the TAA (VEGF -460/-1154/-2578) and CAA haplotypes could significantly decrease the risk of developing EP compared with the haplotype of TGC. Conclusion: The -1154A or -2578A alleles of VEGF gene could significantly decrease the risk of EP and might be potentially protective factors for EP development in Chinese women.

Interplay between 3'-UTR polymorphisms in the vascular endothelial growth factor (VEGF) gene and metabolic syndrome in determining the risk of colorectal cancer in Koreans.

BackgroundPolymorphisms in angiogenesis-related genes and metabolic syndrome (MetS) risk factors play important roles in cancer development. Moreover, recent studies have reported associations between a number of 3′-UTR polymorphisms and a variety of cancers. The aim of this study was to investigate the associations of three VEGF 3′-UTR polymorphisms (1451C > T [rs3025040], 1612G > A [rs10434], and 1725G > A [rs3025053]) and MetS with colorectal cancer (CRC) susceptibility in Koreans.MethodsA total of 850 participants (450 CRC patients and 400 controls) were enrolled in the study. The genotyping of VEGF polymorphisms was performed by TaqMan allelic discrimination assays. Cancer risks of genetic variations and gene-environment interactions were assessed by adjusted odds ratios (AORs) and 95% confidence intervals (CIs) of multivariate logistic regression analyses.ResultsVEGF 1451C > T was significantly associated with rectal cancer risk (Dominant model; AOR =1.58; 95% CI = 1.09 - 2.28; p = 0.015) whereas VEGF 1725G > A correlated with MetS risk (Dominant model; AOR =1.61; 95% CI =1.06 - 2.46; p = 0.026). Of the gene-environment combined effects, the interaction of VEGF 1451C > T and MetS contributed to increased rectal cancer risk (AOR = 3.15; 95% CI = 1.74 - 5.70; p < .001) whereas the combination of VEGF 1725G > A and MetS was involved with elevated colon cancer risk (AOR = 2.68; 95% CI = 1.30 - 1.55; p =0.008).ConclusionsOur results implicate that VEGF 1451C > T and 1725G > A may predispose to CRC susceptibility and the genetic contributions may be varied with the presence of MetS.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-881) contains supplementary material, which is available to authorized users.

Vascular endothelial growth factor polymorphisms as effect modifiers of oral squamous cell carcinoma risk: A systematic review and meta-analysis.

Smoking is one of the main risk factors for the development of oral squamous cell carcinoma (OSCC). Smoking may affect single-nucleotide polymorphism (SNP)-dependent vascular endothelial growth factor (VEGF)-induced angiogenic activity. Therefore, we systematically reviewed the published VEGF-SNP genotype data of OSCC patients and healthy individuals and performed a meta-analysis comparing the VEGF-SNP genotypes of smoking and non-smoking patients in association with OSCC incidence. Prospective and retrospective studies on the clinical comparison of OSCC patients with different VEGF-SNP genotypes were reviewed. The meta-analysis re-pooled studies of smoking and non-smoking OSCC patients with different VEGF-SNPs between 2006 and 2014. The identified articles were reviewed and those reporting pertinent information, assignment to smoking and non-smoking patient groups and sufficient data for estimation of an odds ratio (OR) with a 95% confidence interval (CI) were selected for the meta-analysis. Pooled ORs and CIs for the comparison of SNP distribution in the smoking and non-smoking subgroups were calculated and compared using the random-effects model. A total of 7 studies were included in the systematic review, which was followed by a meta-analysis using 3 pertinent studies. The reviewed studies reported discrepant findings, with differences between Asian and European patients. The meta-analysis demonstrated marginal but not statistically significant differences, suggesting that specific VEGF-SNPs may be OSCC risk modifiers for smokers, depending on the ethnic background. The performed meta-analysis suggested an increased OSCC risk for smokers carrying specific VEGF-genotypes, although the calculated data did not reach the level of significance. However, data have to be interpreted with caution due to the limited sample size. Therefore, further studies, including larger patient samples, are mandatory.

Investigation of polymorphisms in pre-eclampsia related genes VEGF and IL1A.

Pre-eclampsia (PE) is a pregnancy-specific multisystemic syndrome characterized by high blood pressure and presence of protein in the urine. The pathogenesis of pre-eclampsia is poorly understood and many factors such as environment, genetic, and immunology may be involved in PE pathophysiology. Among the genetic factors, there is an association between pre-eclampsia and polymorphisms in some genes of different population samples, as vascular endothelial growth factor and interleukin 1 alpha. The vascular endothelial growth factor gene is highly polymorphic and acts as a regulator in endothelial cell proliferation and vascular permeability. The secretion of interleukin 1 alpha leads to a pro-inflammatory cascade, which leads to high levels of circulating cytokines. This high amount of cytokines corroborates to structural and functional alterations in endothelial cells. The aim of this study was to investigate the vascular endothelial growth factor (VEGF) G-634C and interleukin 1 alpha (IL1A) rs3783550 polymorphism in a specific Brazilian pre-eclampsia group. The evaluation of the vascular endothelial growth factor polymorphism was performed by PCR-RFLP restriction enzyme BsmFI and the IL1A polymorphism by allele-specific PCR. Molecular investigation was carried out by fragment size analysis on agarose and/or polyacrylamide gels. However, no relation between polymorphism VEGF G-634C and pre-eclampsia was observed, indicating that further investigations with a larger sampling and other polymorphisms are still required. On the other hand, the rs3783550 polymorphism in the interleukin 1 alpha gene is correlated to pre-eclampsia, indicating that women with the allele A have a higher probability of developing the disease. Thus, the interleukin 1 alpha gene could be used as a therapeutic tool for the diagnosis, as well as for monitoring the patients.

Role of vascular endothelial growth factor polymorphisms (-2578C>A, -460 T>C, -1154G>A, +405G>C and +936C>T) in endometriosis: a case-control study with Brazilians.

BackgroundEndometriosis is regarded as a complex and heterogeneous disease in which genetic and environmental factors contribute to the phenotype. The Vascular Endothelial Growth Factor (VEGF) plays important roles in the pathogenesis of endometriosis. The present study was aimed at investigating the contribution of VEGF polymorphisms as risk factors for the development of endometriosis. This is the first study to evaluate the combined influence of the five most common VEGF polymorphisms.MethodsThis study was conducted at two hospitals from the Brazilian public health system, and comprised 294 women submitted to laparoscopic or laparotomy surgery: 182 patients had a histologically confirmed diagnosis of endometriosis (cases), whereas 112 had no evidence of the disease (controls). The VEGF polymorphisms were determined by TaqMan real-time polymerase chain reaction. The odds ratio (OR) with their 95% confidence intervals (CI) were calculated using an unconditional logistic regression model.ResultsEndometriosis patients and controls did not differ regarding age distribution, whereas the body mass index was significantly lower in endometriosis patients, when compared with controls (23.1 ± 3.9 versus 27.3 ± 5.9, P < 0.001). The evaluation of gynecological symptoms, including dysmenorrhea, non-cyclic chronic pelvic pain, dyspareunia and infertility, indicates significantly higher prevalences among endometriosis cases. The variant allele -1154A was significantly associated with endometriosis, either considering all cases (OR: 1.90, 95% CI: 1.23–2.97), deep infiltrating endometriosis (DIE) (OR: 1.83, 95% CI: 1.16-2.90) or moderate and severe endometriosis (stages III-IV) (OR: 1.97, 95% CI: 1.21-3.19). No significant differences were found in allele or genotype distributions of the –2578C > A, -460 T > C, +405G > C and +936C > T polymorphisms between endometriosis cases and controls. A total of six haplotypes were inferred derived from four polymorphisms (-2578C > A, -460 T > C, -1154G > A and +405G > C). There was a protective association between CCGG haplotype and endometriosis, either considering all cases (OR: 0.36, 95% CI: 0.15–0.86), DIE (OR: 0.37 95% CI: 0.15 – 0.90) or stages III-IV (OR: 0.35 95% CI: 0.13 – 0.95).ConclusionsThe present results indicate a positive association between VEGF -1154G > A and the risk of developing endometriosis, whereas the CCGG haplotype may be protective against the development of disease.

Association of vascular endothelial growth factor – A gene polymorphisms and haplotypes with breast cancer metastases

Background. Vascular endothelial growth factor (VEGF-A) is a key regulator of tumor-induced angiogenesis and essential for tumor growth and distant tumor spread. The aim of the present study was to evaluate the role of VEGF-A polymorphisms and haplotypes for metastatic progression in breast cancer patients.Material and methods. We performed a prospective study including 801 breast cancer patients. Occurrence of metastases was examined in regular follow-up investigations. Seven VEGF-A polymorphisms were selected and determined by 5′-nuclease assays (TaqMan). The selection of VEGF-A variants was based upon their location (promoter or UTR) as well as a minor allele frequency of at least 0.10. Haplotypes and linkage disequilibrium were determined using the Haploview program.Results. Within a median follow-up time of 84 months, 165 (21%) patients developed distant metastases. In univariate analysis, carriers of the CCCCC haplotype formed by five polymorphisms upstream the coding region were at decreased risk of distant metastases [hazard ratio (HR) = 0.743; 95% CI 0.579–0.953; p = 0.019]. Univariate analysis also revealed a decreased risk of distant metastases for postmenopausal patients carrying the -634G> C polymorphism (HR 0.704; 95% CI 0.514–0.965; p = 0.029) and the CCCCC haplotype (HR = 0.645; 95% CI 0.464–0.898; p = 0.009). After adjustment for other co-variates, the HR for distant metastases was 0.651 (95% CI 0.447–0.948) for postmenopausal carriers of the -634G> C polymorphism (p = 0.025; corrected p-value = 0.262), and 0.586 (95% CI 0.393–0.873) for postmenopausal patients with the CCCCC haplotype (p = 0.009, corrected p-value = 0.189).Conclusion. The results from univariate and multivariate analyses suggest an influence of VEGF-A gene variants on the development of distant metastases in breast cancer patients. However, none of the observed associations reached statistical significance after correction for the effects of multiple testing. Additional prospective and sufficiently powered studies are essential before firm conclusions about the role of VEGF-A gene variants for distant progression in breast cancer can be drawn.

Investigating the association of vascular endothelial growth factor polymorphisms with breast cancer: a Moroccan case-control study.

The main mediator of breast cancer (BC) angiogenesis is the vascular endothelial growth factor (VEGF). Variation of VEGF-A gene may influence the BC susceptibility. The present case-control study investigated the association of the four commonly studied single nucleotide polymorphisms (SNP) of VEGF-A, namely: -1154A/G (rs1570360), -2578C/A (rs699947), -634G/C (rs2010963) and -460T/C (rs833061) with BC susceptibility and aggressiveness in Moroccan women. After genomic DNA extraction, genotyping was performed by TaqMan SNP assays on 70 BC patients and 70 healthy women. The χ2 test was used to detect differences in the genotype frequencies of VEGF between the groups and to stratify genotypes by the clinico-pathological characteristics in patient's group. Women carriers of -1154AG + AA and -2578AC + AA VEGF genotypes had a reduced risk to develop BC [p = 0.018, OR 2.25 95 % CI (1.14-4.42) and p = 0.022, OR 2.26 95 % CI (1.12-4.58), respectively]. Carriers of -460CT and CT + CC genotypes had also a reduced risk to develop BC [p = 0.045, OR 2.63 95 % CI (1.19-5.84) and p = 0.043, OR 2.12 95 % CI (1.01-4.43), respectively]. Moreover, the A-1154A-2578G-634C-460 haplotype seems to have a protective effect against BC risk [p = 0.007, OR 2.41 95 % CI (1.27-4.55)]. Stratification for BC patients according to clinico-pathological characteristics reveals no association with any of VEGF-A SNPs. In conclusion, the data indicated significant associations of VEGF -1154A/G, -2578C/A and -460T/C polymorphisms with BC susceptibility in Moroccan individuals. These VEGF-A polymorphisms can be useful as predisposing genetic markers for BC. Further larger-scale studies are necessary to confirm our finding.

Vascular endothelial growth factor (VEGF-634G/C) polymorphism and retinopathy of prematurity: a meta-analysis

PurposeVascular endothelial growth factor polymorphism (VEGF-634G/C, rs 2010963) has been considered a risk factor for the development of retinopathy of prematurity (ROP). However, the results remain controversial. Therefore, the aim of the present meta-analysis was to determine the association between VEGF-634G/C polymorphism and ROP risk. MethodsPublished literature from PubMed and other databases were retrieved. All studies evaluating the association between VEGF-634G/C polymorphism and ROP risk were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random or fixed effects model. A total of six case-control studies including 355 cases and 471 controls were included. ResultsBy pooling all the studies, we found that VEGF-634G/C polymorphism was not associated with ROP risk at co-dominant and allele levels and no association was also found in dominant and recessive models. While stratifying on ethnicity level no association was observed in Caucasian and Asian population. DiscussionThis meta-analysis suggests that VEGF-634G/C polymorphism may not be associated with ROP risk, the association between single VEGF-634G/C polymorphism and ROP risk awaits further investigation.

Association of the vascular endothelial growth factor -2578C/A polymorphism with cancer risk: A meta-analysis update

The vascular endothelial growth factor (VEGF) -2578C/A polymorphism has been previously reported to be associated with cancer risk; however, the results have been controversial. Therefore, the aim of the present study was to explore the association between the VEGF -2578C/A polymorphism with the cancer risk. A total of 37 case-control studies were identified. The pooled analysis showed that there was no association between VEGF -2578C/A and the risk of cancer, and the odds ratios (ORs) [with the corresponding 95% confidence intervals (95% CIs)] were 0.97 (0.91-1.04) for C vs. A, 0.94 (0.86-1.02) for CC vs. AA, 0.92 (0.80-1.06) for CA vs. AA, 0.96 (0.89-1.03) for CC/CA vs. AA and 0.97 (0.88-1.08) for CC vs. CA/AA. Subgroup analyses according to ethnicity, source of control and type of cancer showed that the VEGF -2578C/A polymorphism is associated with colorectal and lung cancers. Additionally, the polymorphism may decrease the risk of cancer in the Asian population. This VEGF polymorphism was not associated with a risk of cancer for the Caucasian [0.92 (0.76-1.11) for CC vs. AA] and African populations [1.31 (0.67-2.58) for CC vs. AA], and it was not associated with bladder [1.06 (0.74-1.53) for CC/AA] and breast cancers [1.01 (0.90-1.15) for CC/AA]. Therefore, the present meta-analysis indicates that VEGF -2578C/A may only be associated with the risk of colorectal cancer, lung cancer and the Asian population. More studies with larger sample sizes are required to provide more conclusive evidence.

Association of vascular endothelial growth factor polymorphisms with clinical outcome of renal cell carcinoma patients.

We investigated the association of three single nucleotide polymorphisms (SNPs) in VEGF gene with the prognosis of renal cell carcinoma (RCC) and its association with clinical characteristics of RCC, such as tumor stages, metastasis, and tumor size. Polymerase chain reaction (PCR) restriction fragment length polymorphism analysis was used to genotype specimens for three polymorphisms (-2578C/A, -1154G/A, and -634G/C) in the VEGF gene. Hazard ratios (HRs) and their confidence intervals (CIs) were used to analyze the association of three SNPs in the VEGF gene with survival time using a multivariate Cox proportional hazards model. Frequencies of VEGF-2578AA genotype and A allele were significantly higher in patients with III-IV tumor stage or larger tumor size when compared with CC genotype. Moreover, frequencies of VEGF-634CC genotype and C allele were significantly higher in patients with tumor size >4 cm when compared with -634GG genotype. By Cox proportional hazards model, patients carrying VEGF-2578AA genotype and A allele significantly increased the risk of death from RCC, with the adjusted HRs (95 % CI) of 2.23 (1.15-4.36) and 1.55 (1.11-2.17), respectively. Our study suggests that VEGF-2578C/A and VEGF-634G/C polymorphisms may have effects on the prognosis of RCC. This finding might help in clarifying the mechanisms of RCC development and progression.

The -1154 G/A VEGF gene polymorphism is associated with the incidence of basal cell carcinoma in patients from northern Poland.

Vascular endothelial growth factor (VEGF) is believed to play a crucial role in neoplastic angiogenesis. Although the genetic background of basal cell carcinoma (BCC) has been analyzed in some papers, the mechanism of BCC pathogenesis is not fully understood. To the best of our knowledge, VEGF gene polymorphisms have not yet been explored. The aim of the study was to asses the frequency of three polymorphisms in the VEGF gene (−1154 G/A, −460 T/C and +405 G/C) in patients of Polish origin with BCC and control group. In addition, VEGF serum levels of patients with BCC and controls were measured. The study involved 180 patients (96 women, 84 men) with BCC and a mean age of 68.9 ± 11.8, and 215 healthy age- and sex-matched volunteers. The VEGF polymorphisms at positions −1154 and +405 were analyzed using the amplification refractory mutation system polymerase chain reaction method. To assess the VEGF gene polymorphism at position −460, we used the polymerase chain reaction restriction fragment length polymorphism method. Serum levels of VEGF protein were measured using the ELISA test. The presence of the G allele (GA or GG) in the −1154 VEGF polymorphism was associated with an increased risk of BCC development (OR = 7.28, p < 0.0001). Furthermore, the carriers of the AA genotype in −1154 VEGF polymorphism showed significantly reduced risks of BCC (OR = 0.14, p < 0.0001). It was also shown that the GTC haplotype of VEGF predisposes to BCC development (OR = 1.69, p = 0.013), while the presence of the ATG haplotype significantly reduces this risk (OR = 0.17, p = 0.00001). We have found significantly increased VEGF serum levels among BCC patients, in comparison with the healthy controls (mean 596.7 ± 393.5 pg/ml; range 60.1–931.4 vs. 255.9 ± 174.6 pg/ml; range 42.2–553.0 pg/ml; p < 0.0004). The serum levels of VEGF significantly correlated with tumor size: r = 0.41, p < 0.0001. Our results testify to the importance of −1154 G/A VEGF gene polymorphisms in altering the risk of BCC among the population from northern Poland.

Association between vascular endothelial growth factor gene polymorphisms and bladder cancer risk.

Vascular endothelial growth factor (VEGF) gene polymorphisms are associated with susceptibility to a number of cancers. The present case-controlled study aimed to investigate the correlation between VEGF gene polymorphisms and the risk of bladder cancer. The effects of VEGF polymorphisms were investigated in patients with bladder cancer and healthy controls in our hospital between May, 2008 and May, 2013. Peripheral blood samples were obtained from 480 patients with bladder cancer and 420 healthy controls. The polymerase chain reaction-restriction fragment length polymorphism technique was used to detect three VEGF gene polymorphisms (rs3025039 C/T, rs833052 C/A and rs1570360 G/A) in these subjects. The genotype and allele frequencies were also investigated in order to determine their association with stage, grade and histological type of bladder cancer, as well as smoking status. Our results suggested that the frequency of the rs833052 AA genotype was significantly higher in patients with bladder cancer [odds ratio (OR)=1.75; 95% confidence interval (CI): 1.05-2.92; P=0.03] compared to that in healthy controls. There was no significant correlation between the rs833052 AA genotype and bladder cancer stage, grade or histological type, whereas smoking was identified as a risk factor for bladder cancer in the included patients (OR=1.48; 95% CI: 1.13-1.93; P=0.004). The rs3025039 and rs1570360 gene polymorphisms were not found to be correlated with the risk of bladder cancer or its progression. In conclusion, our results suggested that the VEGF rs833052 C/A polymorphism may be associated with a modest increase in the risk of bladder cancer in Chinese individuals.

Vascular endothelial growth factor polymorphism +405 G/C is associated with early stage of diabetic nephropathy in patients with type 2 diabetes

Vascular endothelial growth factor polymorphism +405 G/C is associated with early stage of diabetic nephropathy in patients with type 2 diabetes

Roles of Three Common VEGF Polymorphisms in the Risk of Age-Related Macular Degeneration

Associations between vascular endothelial growth factor (VEGF) polymorphisms (rs833061, rs1413711, and rs3025039) and risk of age-related macular degeneration (AMD) have been extensively studied, but the currently available results are contentious rather than conclusive. Therefore, we performed the present meta-analysis to further assess the associations. Literature search in PubMed, Embase, and Web of Science databases was conducted until April 2013. The strength of the associations between VEGF polymorphisms and AMD risk was estimated by pooled odds ratios (ORs) and 95% confidence intervals (CIs). Both models of fixed effects and random effects were performed to summarize the pooled ORs. All data were analyzed by Stata software 12.0. The meta-analysis results based on nine case-control studies with 2427 cases and 2037 controls showed that rs833061 had protective effects on AMD risk (TT vs. CT+CC: OR=0.58, 95% CI=0.41-0.81), whereas rs1413711 (TT vs. CT+CC: OR=1.46, 95% CI=1.10-1.93) and rs3025039 (TT vs. CC: OR=1.87, 95% CI=1.15-3.02; TT vs. CT+CC: OR=2.09, 95% CI=1.30-3.37) represented as risk factors for AMD. Subgroup analysis by ethnicity suggested significantly reduced risk in Caucasians (TT vs. CT+CC: OR=0.60, 95% CI=0.36-0.99; T vs. C: OR=0.89, 95% CI=0.78-1.00) and Asians (TT+CT vs. CC: OR=0.57, 95% CI=0.34-0.96; TT vs. CT+CC: OR=0.54, 95% CI=0.33-0.90) for rs833061, yet elevated risk in Caucasians (TT vs. CT+CC: OR=2.05, 95% CI=1.24-3.38) for rs1413711 and in Asians (TT vs. CC: OR=2.06, 95% CI=1.24-3.43; TT vs. CC: OR=2.34, 95% CI=1.42-3.89) for rs3025039. In stratified analysis by type of AMD, rs833061 was observed to decrease wet AMD risk, while rs1413711 and rs3025039 were found to increase the risk of wet AMD. Based on the currently available data, this meta-analysis suggests that the VEGF polymorphisms may be associated with risk of AMD, particularly wet AMD.

Associations of VEGF and VEGFR2 polymorphisms with increased risk and aggressiveness of multiple myeloma

Angiogenesis has been highlighted as a critical component in the progression of multiple myeloma (MM), and vascular endothelial growth factor (VEGF) as well as its type 2 receptor (VEGFR2) are thought to play a major role in the process. Single nucleotide polymorphisms (SNPs) have been described in VEGF and VEGFR2 genes, with quantitative or qualitative changes in encoded VEGF and VEGFR2. The roles of VEGF -2578C/A, -1154G/A, and -634G/C as well as VEGFR2 -604T/C and +1192G/A SNPs in the risk and manifestations of MM are still unknown; therefore, this study aimed to clarify this issue. DNA from 192 patients and 209 controls were analyzed by real-time polymerase chain reaction for identification of genotypes. The frequencies of VEGF -2578CC, VEGF -2578CC plus VEGF -634GG, and VEGF -2578CC plus VEGF -1154GG plus VEGF -634GG genotypes were higher in patients than in controls. Carriers of the respective genotypes had a 1.89-, a 5.52-, and a 4.91-fold increased risk for MM than others. VEGF -2578CC plus VEGFR2 +1192GG, VEGF -2578CC plus VEGF -634GG plus VEGFR2 +1192GG, and VEGF -1154GG plus VEGF -634GG plus VEGFR2 -604TT combined genotypes were more common in patients than in controls. Carriers of the respective genotypes had a 2.56-, a 10.97-, and a 14.10-fold increased risk for MM than others. An excess of VEGFR2 -604TT genotype was also seen in patients with stage II or III tumors when compared with those with stage I tumors. Our data suggest, for the first time, that inherited abnormalities in VEGF and VEGFR2 pathways influence the risk and aggressiveness of MM.

Four Polymorphisms ofVEGF(+405C&gt;G, −460T&gt;C, −2578C&gt;A, and −1154G&gt;A) in Susceptibility to Psoriasis: A Meta-Analysis

The contribution of genetic polymorphisms in the vascular endothelial growth factor (VEGF) gene to psoriasis risk is a controversial topic. The aim of this meta-analysis was to investigate large-scale evidence to determine the degree to which four common VEGF polymorphisms (+405C>G [dbSNP: rs2010963], -460T>C [dbSNP: rs833061], -2578C>A [dbSNP: rs699947], and -1154G>A [dbSNP: rs1570360]) are associated with susceptibility to psoriasis. A literature search of PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure, and Chinese Biomedical Literature Database was conducted to identify all eligible studies published before September 15, 2013. The principal outcome measure for evaluating the strength of the association was crude odds ratios (ORs) along with their corresponding 95% confidence intervals (95% CIs). Two thousand five hundred thirty-one patients and 2670 controls from nine case-control studies detailing a possible association between the VEGF genotypes and psoriasis risk were selected. Our meta-analysis provides evidence that two independent alleles +405G and -460C may be a protective factor for psoriasis in Asians, whereas the -1154A allele had a slight but statistically significant preventive effect on the development of psoriasis in Caucasians. The -2578C>A polymorphism, however, did not correlate with any significant difference between patients and healthy controls, even when the groups were stratified by ethnicity. Results from the meta-analysis do support the hypothesis that single-nucleotide polymorphism markers at +405C>G, -460C>T, and -1154G>A of the VEGF gene may serve as biological markers of psoriasis. Future studies should investigate interactions among multiple genotypes and environmental exposures to identify the role of proangiogenic markers in psoriasis and to delineate the underlying mechanisms of psoriasis.