VEGF Polymorphisms Research Articles

Association of VEGFA gene polymorphisms with susceptibility to non-Hodgkin's lymphoma: Evidences from population-based and in silico studies

Vascular endothelial growth factors (VEGF) regulate hematological tumors progression. This study was aimed to assess the relationship between two VEGFA polymorphisms, C−2578A and G+405C, and the risk of non-Hodgkin's lymphoma (NHL). Blood samples were collected from a total of 246 subjects. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used for genotyping. A novel in silico analysis was performed to predict the potential functions of the SNPs. CA genotype of C−2578A polymorphism was associated with NHL. We found that codominant, dominant and over-dominant inheritance models of this SNP were significantly associated with this hematological disorder. No significant link found between G+405C polymorphism and NHL risk. However, the presence of the mutant alleles of VEGFA G+405C and C−2578A polymorphisms could provide new binding sites for nuclear transcription factors. In our study, the C−2578A polymorphism conferred an increased risk of NHL. The mutant allele of this variant might affect VEGFA transcriptional activity.

Association of angiogenesis and inflammation-related gene functional polymorphisms with early-stage breast cancer prognosis.

Genetic variations in inflammation- and angiogenesis-related genes may alter the coded protein level and impact the pathogenesis of breast cancer (BC). The present study investigated the association of functional single nucleotide polymorphisms (SNPs) in the VEGFA, IL-1β, IL-1α and IL-6 genes with the early-stage BC phenotype and survival. Genomic DNA and clinical data were collected for 202 adult Eastern European (Lithuanian) women with primary I–II stage BC. Genotyping of the SNPs was performed using TaqMan SNP genotyping assays. Nine VEGFA, IL-1β, IL-1α and IL-6 polymorphisms were analysed. The VEGFA and IL-6 haplotypes were inferred using Phase software. Patients were prospectively followed-up for recurrence, occurrence of metastasis and mortality until April 30, 2019. All studied genotypes were in Hardy-Weinberg equilibrium and had the same distribution as the 1,000 Genomes project Phase 3 dataset for European population. Significant associations of the studied SNPs with clinicopathologic variables were observed between IL-1α rs1800587 C allele and larger primary tumour size; IL-6 rs1800797 A allele, rs1800797 GA genotype, rs1800795 C allele, IL-6 (rs1800797-re1800795) AC diplotype and hormonal receptor-positive disease; IL-6 rs1800797 A allele and HER2 negative status. In univariate Cox survival analysis, IL-1α rs1800587 CC and IL-6 rs1800797 GG genotype carriers exhibited worse disease-free survival (DFS), metastasis-free survival (MFS) and overall survival (OS). The IL-6 rs1800795 GG genotype was associated with worse OS. IL-6 (rs1800797, rs1800795) GG/GG diplotype carriers had shorter MFS and OS. Multivariate Cox survival analysis revealed that the IL-1α rs1800587 CC genotype was an independent negative prognostic factor for DFS, MFS and OS, and the IL6 GG/GG diplotype was an independent negative prognostic factor for MFS and OS. According to the present study, functional SNPs in the IL-1α and IL-6 genes may contribute to the identification of patients at higher risk of BC recurrence, development of metastases and worse OS among early-stage patients with BC.

Association of vascular endothelial growth factor A polymorphisms and aberrant expression of connexin 43 and VEGFA with idiopathic recurrent spontaneous miscarriage.

Idiopathic recurrent spontaneous miscarriage (IRSM) is one of the pregnancy outcomes that affects 1-2% of women trying to conceive. Specific genotype or aberrant expression of vascular endothelial growth factor A (VEGFA) and connexin 43 (Cx43) as two important genes for embryonic development are deemed to increase the risk of IRSM. To investigate any possible association of VEGFA polymorphisms and aberrant expression of Cx43 and VEGFA with IRSM, we carried out a case-control study including embryo chorionic villus tissues of 100 pregnant women with IRSM and 100 embryo chorionic villus tissues of healthy pregnant women without history of miscarriage. Restriction fragment length polymorphism was used for genotyping of rs699947 (-2578C/A) and rs2010963 (-634G/C) polymorphisms in VEGFA. Besides, quantitative real-time PCR was performed for VEGFA and Cx43 expression analysis. The results showed that the frequency of -634G/C and C/C genotypes was significantly higher in aborted fetuses (P = 0.001 and P < 0.001, respectively) compared to the control group's. However, the frequency of -2578C/A genotypes was not significantly different between the cases and controls. Moreover, a significant higher expression of VEGF (P = 0.0005) and Cx43 (P = 0.0011) was observed in chorionic villus tissues of women with IRSM. The finding demonstrated that IRSM frequency may depend on GC and CC genotypes of rs2010963 VEGF polymorphism and expression level of VEGF and Cx43 in IRSM patients was increased.

Epistasis of polymorphisms related to the articular cartilage extracellular matrix in knee osteoarthritis: Analysis-based multifactor dimensionality reduction.

Osteoarthritis (OA) is a complex disease with a multifactorial etiology. The genetic component is one of the main associated factors, resulting from interactions between genes and environmental factors. The aim of this study was to identify gene-gene interactions (epistasis) of the articular cartilage extracellular matrix (ECM) in knee OA. Ninety-two knee OA patients and 147 healthy individuals were included. Participants were genotyped in order to evaluate nine variants of eight genes associated with ECM metabolism using the OpenArray technology. Epistasis was analyzed using the multifactor dimensionality reduction (MDR) method. The MDR analysis showed significant gene-gene interactions between MMP3 (rs679620) and COL3A1 (rs1800255), and between COL3A1 (rs1800255) and VEGFA (rs699947) polymorphisms, with information gain values of 3.21% and 2.34%, respectively. Furthermore, in our study we found interactions in high-risk genotypes of the HIF1AN, MMP3 and COL3A1 genes; the most representative were [AA+CC+GA], [AA+CT+GA] and [AA+CT+GG], respectively; and low-risk genotypes [AA+CC+GG], [GG+TT+GA] and [AA+TT+GA], respectively. Knowing the interactions of these polymorphisms involved in articular cartilage ECM metabolism could provide a new tool to identify individuals at high risk of developing knee OA.

The Comparison of VEGF Polymorphism Frequency between Cases with Low and High Ovarian Reserve

Amaç: Vasküler endotelyal büyüme faktörü (VEGF), overyan anjiogenezde kilit rol oynayan bir sitokindir. Biz de çalışmamızda düşük ve yüksek over rezervli infertil kadınlarda VEGF gen polimorfizminin over rezervi ile olası ilişkisini araştırmayı amaçladık.Gereç ve Yöntemler: Bu çalışmaya, polikistik over sendromlu (PCOS) 64 kadın ile prematür overyan yetmezlikli (POF) 30 kadın dahil edildi. Periferik venöz kan örneklerinden elde edilen DNA’da polimeraz zincir reaksiyonu (PCR) yöntemi ile VEGF geni-2578 C/A tek nükleotid polimorfizmi (SNP) incelendi. İstatistiki analiz SPSS 16.0 programı ile yapıldı.Bulgular: PCOS ve POF gruplarının ortalama yaş, vücut kitle indeksi, TSH ve prolaktin seviyeleri yönünden anlamlı bir fark yoktu. PCOS grubu için genotip dağılımı %56.2 CC, %26.6 CA ve %17.2 AA iken, POF grubu için ise %26.7 CC %53.3 CA ve %20 AA idi. Gruplar arasında genotip frekansları bakımından farklılık saptandı (p = 0.018). Mutant A allelinin, over rezervini minimal azaltıcı etkisi olduğu gözlendi (95%CI= 0.12-0.22, OR: 0.5, p&amp;lt;0.01).Sonuç: Çalışmamızda gözlediğimiz VEGF -2578 C/A polimorfizmindeki mutant A allelinin over rezervi üzerine olan etkisini tartışmak için genişletilmiş popülasyon çalışmalarına ihtiyaç vardır.

VEGF-A and ICAM-1 Gene Polymorphisms as Predictors of Clinical Outcome to First-Line Bevacizumab-Based Treatment in Metastatic Colorectal Cancer.

Bevacizumab is used to treat metastatic colorectal cancer (mCRC). However, there are still no available predictors of clinical outcomes. We investigated selected single nucleotide polymorphisms (SNPs) in the genes involved in VEGF-dependent and -independent angiogenesis pathways and other major intracellular signaling pathways involved in the pathogenesis of mCRC as an attempt to find predictors of clinical outcome. Forty-six patients treated with first-line bevacizumab-based chemotherapy were included in this study with a 5 year follow up. Genomic DNA was isolated from whole blood for the analysis of VEGF-A (rs2010963, 1570360, rs699947), ICAM-1 (rs5498, rs1799969) SNPs and from tumor tissue for the detection of genomic variants in KRAS, NRAS, BRAF genes. PCR and next generation sequencing were used for the analysis. The endpoints of the study were progression-free survival (PFS) and overall survival (OS). The VEGF-A rs699947 A/A allele was associated with increased PFS (p = 0.006) and OS (p = 0.043). The ICAM-1 rs1799969 G/A allele was associated with prolonged OS (p = 0.036). Finally, BRAF wild type was associated with increased OS (p = 0.027). We identified VEGF-A and ICAM-1 variants in angiogenesis and other major intracellular signaling pathways, such as BRAF, that can predict clinical outcome upon bevacizumab administration. These identified biomarkers could be used to select patients with mCRC who may achieve long-term responses and benefit from bevacizumab-based therapies.

Associations of VEGFA and KDR single-nucleotide polymorphisms and increased risk and aggressiveness of high-grade gliomas.

Angiogenesis, induced by the vascular endothelial growth factor A through its ligation to the vascular endothelial growth receptor 2, has been described as a crucial point in high-grade glioma development. The aim of this study was to evaluate the influence of VEGFA-2578C/A, -2489C/T, -1154G/A, -634G/C, and -460C/T, and KDR-604T/C, -271G/A, +1192G/A, and +1719A/T single-nucleotide polymorphisms on risk and clinicopathological aspects of high-grade glioma. This case-control study enrolled 205 high-grade glioma patients and 205 controls. Individuals with VEGFA-2578 CC or CA, VEGFA-1154 GG, VEGFA-634 GC or CC, and VEGFA-460 CT or TT genotypes were under 2.56, 1.53, 1.54, and 1.84 increased risks of high-grade glioma, compared to others, respectively. And 1.61, 2.66, 2.52, 2.53, and 2.02 increased risks of high-grade glioma were seen in individuals with VEGFA-2578 CC plus VEGFA-1154 GG, VEGFA-2578 CC or CA plus VEGFA-634 GC or CC, VEGFA-2578 CC or CA plus VEGFA-460 CT or TT, VEGFA-1154 GG or GA plus VEGFA-634 GC or CC, and VEGFA 634 GC or CC plus VEGFA-460 CT or TT combined genotypes, respectively, when compared to others. The "CAGT" haplotype of KDR single-nucleotide polymorphisms was more common in patients with grade IV than in those with grade III tumors, and individuals carrying this haplotype were at 1.76 increased risk of developing grade IV tumors than others. We present, for the first time, preliminary evidence that VEGFA-2578C/A and VEGFA-1154G/A single-nucleotide polymorphisms increases high-grade glioma risk, and "CAGT" haplotype of the KDR gene alters high-grade glioma aggressiveness and risk of grade IV tumors in Brazil.

Association of –634 G > C VEGF-A polymorphism in thyroid cancer patients in North West of Iran

Thyroid tumors with prevalence of 10–67% in the world are common among adults. Before the tumor can grow >1–2 mm, it needs blood vessels to supply nutrients and oxygen. The producing of vascular endothelial growing factor by the tumor, stimulates the angiogenesis pathway and producing new blood vessels around the tumor. It is therefore considered as a factor in the prognosis and development of thyroid tumors. The present study investigated VEGF (− 634G > C) gene polymorphism with thyroid tumors susceptibility in the northwest of Iran. This study was performed on 112 patients with thyroid tumors and 132 normal control subjects from Iranian-Azeri population in a case-control study. Genomic DNA was extracted from peripheral blood by salting out method. The genotypes were also determined by PCR-RFLP method. The Alibaba and RNA secondary structure analysis were used to predict that how the binding of some transcription factors affected by this polymorphism. This study indicated that VEGF (− 634G > C) polymorphism in over dominant model (P = .002) was significantly associated with increased risk of thyroid tumors. Moreover, the recessive model of this polymorphism (P = .002) had a protective effect against thyroid tumors. It was found that the sp1 transcription factor binding to −634 position was influenced in presence of G and C alleles of this polymorphism. The results of this study showed that the VEGF −634G > C SNP may be associated with the susceptibility to thyroid tumors in the northwest of Iran. It is also found that how G allele of this polymorphism can be increase the VEGF translation. If these results are confirmed in larger studies, the analysis of the VEGF (−634G > C) (rs2010963) gene polymorphism can be useful in determining the relative risk of tumor development.

Gene polymorphisms in VEGFA and COL2A1 are associated with response to inhaled corticosteroids in children with asthma.

Aim: The purpose of this study was to investigate the involvement of single-nucleotide polymorphisms in VEGFA, TBX21 and COL2A1 in the response to inhaled corticosteroids in asthmatic children. Subjects & methods: Children with mild-to-moderate asthma were enrolled in the study. The SEQUENOM MassARRAY method was used to sequence 27 SNP genotypes. By ranking the data from smallest to largest, we could infer whether the change in distribution of forced expiratory volume in one second/forced vital capcacity (FEV1/FVC) and fractional exhaled nitric oxide differed between genotype groups. Results:VEGFA rs3025039 T allele carriers had a smaller change in FEV1 than CC carriers (p=0.040), and in COL2A1 rs3809324, the frequency of T allele carriers was lower than that of GG carriers (p=0.048). rs3025039 was also associated with changes in FEV1/FVC (p=0.016). Conclusion:VEGFA and COL2A1 polymorphisms are significantly associated with the response to inhaled corticosteroids in asthmatic children.

Associations Between Gene Polymorphisms of Vascular Endothelial Growth Factor and Prostate Cancer.

The aim of this study was to evaluate the association between selected polymorphisms of the vascular endothelial growth factor gene (rs699947, rs144854329, rs833061, rs2010963, rs3025039) and the risk of prostate cancer development and progression. The present study included 446 patients with prostate cancer and 241 healthy men. Genotyping was performed by polymerase-chain reaction-restriction fragment length polymorphism analysis. No significant association between the individual polymorphisms studied and the risk of prostate cancer development was detected. A statistically significantly increased risk of prostate cancer development associated with the presence of 9 or 10 risky alleles was found considering the whole group of patients, as well as in patients with low-grade carcinomas (Gleason score <7). Individual polymorphisms of VEGF do not appear to contribute to prostate cancer. However, a combination of risky alleles of the studied polymorphisms significantly increases the risk of prostate cancer in Slovak patients.

Association between VEGFA gene polymorphisms and bleeding complications in patients maintaining therapeutic international normalized ratio.

Aim: This study was designed to identify the possible effects of VEGFA polymorphisms on the occurrence of bleeding complications in patients with mechanical heart valves who have achieved therapeutic international normalized ratio (INR). Materials & methods: 13 SNPs of VEGFA were analyzed. Uni- and multi-variate analyses were conducted to identify associations between polymorphisms and bleeding complications. Results & conclusion: Patients with the CC genotype of rs35410204 had an approximately tenfold higher bleeding complication than those with the T allele. For rs866236, patients who had wild-type homozygotes showed an approximately 2.9-fold higher bleeding complication than C allele carriers. This study demonstrated that bleeding complications during warfarin therapy are associated with VEGFA polymorphisms in patients with mechanical heart valves.

Haplotype analysis of VEGF gene polymorphisms in polycystic ovary syndrome

This study evaluated the association of polymorphisms of VEGF (endothelial vascular growth factor) gene + 936C/T (rs3025039), 1154 G/A (rs 1570360) and −2578 C/A (rs 699947) in patients with polycystic ovary syndrome (PCOS) and to perform the haplotypes formed by the alleles in the Brazilian population. A total of 110 women without PCOS and 112 women with PCOS were included in the study. Genotyping analyses were performed using the PCR-RFLP assays (rs 3025039 and rs 699947) and by allelic discrimination using the real-time PCR technique (rs 1570360). In the univariate analysis, we observed a significant difference between the groups for the polymorphism rs 1570360 and this polymorphism presented statistical differences between the groups for the recessive model (p = .04). The frequency of the T-G-C haplotype showed a statistically significant difference between women with PCOS and controls (p = .05). The −2578 A/C polymorphism was more frequent in the control group, which may be associated with a protective characteristic for the PCOS manifestation. In the sample analysis, polymorphism rs 1570360 is associated with PCOS and the T-G-C haplotype could be associated with protective factors.

Effect of gene polymorphisms in ADAM33, TGFβ1, VEGFA, and PLAUR on asthma in Thai population.

Most of the asthma susceptibility genes have demonstrated moderate effect. Gene-gene interaction may play a role in asthma. To investigate the genetic and gene-gene interaction effects of single nucleotide polymorphisms (SNPs) in the ADAM33, TGFβ1, VEGFA, and PLAUR genes on asthma in Thai population. Two hundred and fifty control and 250 asthmatic Thai subjects were recruited. Asthma was diagnosed based on symptoms and spirometry assessments using criteria outlined by the American Thoracic Society. Degrees of asthma severity were determined according to guidelines provided by the Global Initiative for Asthma. Asthmatic subjects were subcategorized into the low-severity (n = 106) and high-severity (n = 144) groups. Eleven SNPs in four genes were genotyped, including ADAM33 SNPs (rs528557/S2, rs598418, rs44707/ST+4), TGFβ1 SNPs (rs2241715, rs11466345), VEGFA SNPs (rs833069, rs3025010), and PLAUR SNPs (rs344781, rs344787, rs2239374, rs2239372). Association analyses between SNPs and asthma, and tests for gene-gene interaction were performed. The ADAM33 rs528557/S2 SNP was found to be associated with asthma according to the additive and dominant models. Comparison between the low-severity group and controls showed the VEGFA rs833069 SNP to be significantly associated with the low-severity group. No gene-gene interactions were observed in this study. The ADAM33 rs528557/S2 and the VEGFA rs833069 SNPs were associated with Thai asthmatics, as well as with other populations worldwide. Further studies are warranted to investigate the use these SNPs as biomarkers for establishing early diagnosis or for predicting future risk of asthma.

Association of vascular endothelial growth factor and soluble fms-like tyrosine kinase-1 polymorphisms with their circulating protein levels in preeclampsia

Introduction: Normal development of placental vascular tree requiring angiogenesis and vasculogenesis is structurally and functionally indispensable for both adequate placental growth and delivery of nutrients from mother to the fetus. Impaired placental angiogenesis has been implicated in the pathophysiology of pregnancy complications which have immediate and long-lasting effects on the mother and her child, such as preeclampsia (PE) and fetal growth restriction. The mechanisms underlying the deregulation of placental angiogenesis in PE include a misbalance between the secretion and activity of pro-angiogenic (vascular endothelial growth factor [VEGF]) and anti-angiogenic (soluble fms-like tyrosine kinase-1 [sFlt-1]) factors. Considering the important roles of VEGF and sflt1 in pregnancy, functional polymorphisms in these genes may be potentially important as genetic markers for susceptibility to PE. Thus, the aim of the study was to screen for the presence of VEGF and sFlt-1 gene polymorphisms and to measure their levels in PE patients and controls of Indian origin. Material and Methods: Fifty each of clinically diagnosed patients and gestational and maternal age-matched normotensive, nonproteinuric controls were recruited after taking informed consent. DNA isolated from blood samples was processed for polymerase chain reaction amplification followed by restriction fragment length polymorphism to screen for the presence of VEGF + 936C/T, sFlt-1 (+4244G/A, −4771G/T, −523C/G) polymorphisms. Serum levels of VEGF-A and sFlt-1 were measured by Sandwich enzyme-linked immunosorbent assay (ELISA). Results: Decreased frequency of wild type genotype with respect to VEGF + 936C/T and sFlt-1 (+4244G/A, −4771G/T, and −523C/G) polymorphisms was seen in patients. ELISA results showed lower VEGF-A (198.43 ± 14.63 pg/ml vs. 235.08 ± 16.72 pg/ml [mean ± standard error of mean]) and higher sFlt-1 levels (2932.81 [1802.33–5760.46] pg/ml vs. 1114.94 [655.03–2694.35] Median [Range]; P

Prevalence of candidate single nucleotide polymorphisms on p53, IL-11, IL-10, VEGF and APOE in patients with repeated implantation failure (RIF) and pregnancy loss (RPL)

Recurrent pregnancy loss (RPL; defined as the loss of three or more consecutive pregnancies) and recurrent implantation failure (RIF; when implantation is not achieved after at least three cycles of IVF) are two of the major challenges that reproductive medicine faces. Some polymorphisms have been identified as possible causes of an increased risk of these diseases. This paper studies the prevalence of the polymorphisms in p53, VEGF, IL-10, IL-11 and APOE in RIF and RPL patients that determines the risk for these pathologies. A total of 255 patients were selected (89 RPL patients, 77 RIF patients and 89 controls) and genotyped for p53-R72P; IL-11-1082-AG; VEGF-1154-AG; IL-10; APOE-R112C; APOE-R158C. Statistically significant differences were found in the prevalence of the E4 isoform (R122-R158) of the APOE gene in RPL patients (p < 0.05), and in RIF patients, the R72P polymorphism of the p53 gene and the 1154-AG of the VEGF gene showed different distribution (p < 0.05). Regarding the p53 and IL-11 studied polymorphisms, PP of p53 gene and GG of IL-11 are more prevalent in RPL patients without reaching statistical significance. In conclusion, our results suggest patients carrying variants in p53 and VEGF would be at risk of RIF, and those carrying variants in APOE gene would suffer RPL.

Influence of polymorphisms in VEGF, ACE, TNF and GST genes on the susceptibility to retinopathy of prematurity among Chinese infants.

To investigate common polymorphisms in VEGF, ACE, TNF and GST genes with retinopathy of prematurity (ROP) risk among Chinese infants. Nine polymorphisms in the above genes were genotyped on 724 advanced cases of ROP and 878 prematurely-born infants of low birth weight who were without any ophthalmologic disease. The frequencies of the polymorphisms were compared between cases and controls to identify the association present, if any. Of the nine polymorphisms, only two showed significant associations: ACE insertion deletion (ID) polymorphism (P=0.031) and TNF -308G/A polymorphism (P<0.001). The former was associated with a reduced ROP risk [ID genotype, adjusted OR (aOR): 0.603, 95%CI: 0.427-0.893, P=0.034; DD genotype, aOR: 0.468, 95%CI: 0.229-0.626, P=0.002], while the latter showed an increased risk (GA genotype, aOR: 1.956, 95%CI: 1.396-2.465, P<0.001; AA genotype, aOR: 2.809, 95%CI: 1.802-4.484, P<0.001). The association was also noted at the allele level (ACE D allele aOR: 0.698, 95%CI: 0.294-0.883, P<0.001; TNF -308A allele aOR: 1.776, 95%CI: 1.446-2.561, P<0.001). The ACE ID polymorphism can protect against ROP development while the TNF -308G/A can increase the risk of the disease among Chinese infants.

Polymorphisms in P53 and VEGFA genes in different subtypes of periorbital hyperpigmentation in a Malaysian Chinese population.

The unknown pathogenesis of periorbital hyperpigmentation makes its treatment difficult. Existing evidence links p53 and VEGFA genes with skin hyperpigmentation. This study was aimed at (i) identifying the clinical pattern of periorbital hyperpigmentation; and (ii) detecting the presence of VEGFA and P53 single nucleotide polymorphism (SNPs) in different subtypes of periorbital hyperpigmentation in Malaysian Chinese. A cross-sectional study was conducted among Malaysian Chinese. Clinical assessments were performed, and medical history was collected. Three regions of p53 and two of VEGFA were amplified by PCR followed by direct sequencing using saliva-extracted DNA. Eighty-four participants were recruited (average age 22.2years). In the majority (n=62), both eyelids were affected. Facial pigmentary, demarcation lines, tear trough and eye bags were not observed. Mixed (pigmented-vascular) was the most common subtype. Thirteen SNPs were found, nine of which are new. Only three out of 13 SNPs showed significant association with periorbital hyperpigmentation presentation. TA genotype in rs1437756379 (p53) was significantly more prevalent among participants with mixed subtype (P=0.011) while AC genotype in rs1377053612 (VEGFA) was significantly more prevalent among pigmented subtype (P=0.028). AA genotype in rs1479430148 (VEGFA) was significantly associated with allergic rhinitis in mixed subtype (P=0.012). Mixed subtype was the most prevalent type of periorbital hyperpigmentation in the study population. Three polymorphisms in p53 and VEGFA genes were statistically linked with different clinical presentations of periorbital hyperpigmentation.

Association of genetic polymorphisms in VEGF -460, -7 and -583 and hematocrit level with the development of idiopathic recurrent pregnancy loss and a meta-analysis.

The present study was performed to investigate whether genetic variants of VEGF are associated with recurrent pregnancy loss (RPL) in Korean women and to provide insight into the role of VEGF in the pathogenesis of RPL development. A cohort of 384 women with idiopathic RPL with a history of two or more uxexplained consecutive early pregnancy losses and 236 control women were recruited from an infertility center of university-teaching hospital in Korea between March 1999 and February 2010. We examined three VEGF polymorphisms (rs833061, rs3025020 and rs25648). Genotyping was assessed by polymerase chain reaction (PCR)-restriction fragment length polymorphism analyses (rs3025020) or real-time PCR (rs833061, rs25648). There was no statistically significant difference in frequency of each three VEGF polymorphic loci between the control and RPL groups. Allele combinations of VEGF rs3025020/rs833061 TT/TC and TT/TC+CC genotypes were associated with an increased frequency of RPL development [odds ratio (OR)=3.525, 95% confidence interval (CI)=1.154-10.767, p=0.027 and OR=3.815, 95% CI=1.256-11.588, p=0.018, respectively]. Haplotype analysis revealed that two allele combinations (rs833061/rs3025020 C-T and rs25648/rs3025020 T-T) were associated with an increased prevalence of RPL (OR=2.548, 95% CI=1.502-4.320, p=0.0004 and OR=16.50, 95% CI=0.976-278.8, p=0.003, respectively). Allele combinations and haplotypes of rs3025020/rs833061 were associated with maternal blood hematocrit (HCT) levels in the RPL group (p=0.048 and 0.006, respectively). The VEGF rs833061/rs3025020 genotype allele was related to the development of RPL and was also associated with maternal blood HCT levels in RPL patients. However, further studies are needed to clarify the exact mechanism of how VEGF and HCT are involved in RPL development.

Single-nucleotide polymorphisms of VEGF-A and VEGFR-2 genes and risk of infantile hemangioma.

Infantile hemangioma (IH) is the most common vascular tumor of childhood and infancy. It is distinguished by rapid proliferation of endothelial cells during the first year of life followed by spontaneous regression thereafter. One of the possible factors responsible for the IH development is vascular endothelial grow factor (VEGF). The purpose of this study was to evaluate the influence of selected polymorphisms in the genes coding for VEGF-A (+405G/C, rs2010963; +936 C/T, rs3025039) and its receptor VEGFR-2 (+1416 T/A, rs1870377; -271G/A, rs7667298) on the susceptibility to infantile hemangioma. We performed a case-control study of 99 Polish children hospitalized due to IH and compared them with matched healthy control subjects. The polymorphisms were ascertained through genotyping by PCR-RFLP assay, PCR-HRM, or the allelic discrimination method. The study revealed a lower odds of infantile hemangioma in individuals with GG genotype or G allele for +405G/C VEGF-A polymorphism (ORdis = 0.52, P=0.023 and ORdis =0.63, P=0.025, respectively). No association was observedfor the remaining VEGF and VEGFR-2 polymorphismsand IH risk. In our study, none of the investigated VEGF-A and VEGFR-2 genes polymorphisms was found to be an independent prognostic marker for infantile hemangioma. However, there is evidence that individuals carrying at least one G allele of +405G/C VEGF-A polymorphism have significantly lower risk of IH.

Can VEGFA and ICAM1 polymorphisms predict response to bevacizumab?

2521Background: Most targeted treatments are associated with biomarkers, predictive of drug response. Although bevacizumab is widely used, there are still no available biomarkers. Given the need of...