Endothelial Growth Factor Gene Polymorphisms Research Articles

Polimorfismo genético do fator de crescimento vascular endotelial G1612A (rs10434) e manifestações neuropsiquiátricas em pacientes com lúpus eritematoso sistêmico

AimTo investigate the relation between vascular endothelial growth factor (VEGF) gene polymorphism in systemic lupus erythematosus (SLE) patients and lupus related neuropsychiatric manifestations. Patients and methodsSixty adult SLE patients recruited from the Rheumatology and Neurology departments of Cairo University hospitals were classified into two groups; Group A: 30 patients with neuropsychiatric manifestations (NPSLE) and Group B: 30 patients without. For both groups the SNP G1612A (rs10434) of the VEGF gene was genotyped by real time polymerase chain reaction (RT‐PCR). ResultsStatistically significant difference was found in genotype and allele frequencies between both groups (AA [70% vs 13.3%, p<0.001] and GG [10% vs 66.7%, p<0.001]). ConclusionPolymorphism in the gene coding for VEGF may be associated with increased incidence of neuropsychiatric lupus in SLE patients.

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

To assess the association of vascular endothelial growth factor (VEGF) gene polymorphisms with ectopic pregnancy (EP) among Chinese women. A case-control study was carried out, which compared 192 women with a history of EP with 210 post-menopausal controls who had two pregnancies but no history of EP for the genotypes of the VEGF gene. Polymorphisms of the VEGF gene including -460C/T, -1154G/A, -2578C/A and +936C/T were determined with a polymerase chain reaction-restriction fragment length polymorphism method. No significant difference was found in the genotypic and allelic distribution of the -460C/T and +936C/T polymorphisms between the two groups. Compared with the GG genotype, the VEGF -1154 AA+GA genotype could significantly decrease the risk of EP (OR=0.61, 95%CI: 0.42-0.87). Compared with the CC genotype, VEGF -2578 AA+CA genotype could significantly reduce the risk of EP (OR=0.66, 95%CI:0.44-0.99). Haplotype analysis suggested that the T-A-A (VEGF -460/-1154/-2578) and C-A-A haplotypes could significantly decrease the risk of EP compared with the T-G-C haplotype (P=0.020, OR=0.41, 95%CI:0.19-0.89, P=0.014, OR=0.29, 95%CI:0.11-0.82). The -1154A or -2578A alleles of the VEGF gene can significantly decrease the risk of EP among Chinese women. The VEGF -460C/T, -1154G/A and -2578C/A polymorphisms showed a linkage disequilibrium. Both T-A-A and C-A-A haplotypes can significantly decrease the risk of EP.

Vascular endothelial growth factor gene polymorphisms and association with age related macular degeneration in Indian patients

BackgroundAge-related macular degeneration (AMD) is an important cause of visual impairment in elderly people. AMD is a multifactorial disease in which both environmental and genetic factors have been implicated. Various single nucleotide polymorphisms (SNPs) have been found to be associated with AMD. AimThis study was aimed to investigate the association of polymorphisms in VEGF genes with age related macular degeneration (AMD) in Indian patients. MethodGenotyping for the VEGF −1154 (G>A), −2578 (C>A), +405 (G>C) and −460 (C>T) SNPs was performed in 100 AMD patients and 100 controls by polymerase chain reaction (PCR), restriction fragment length polymorphism (PCR-RFLP) and sequencing method. ResultsOut of the four SNPs, heterozygous genotypes of VEGF −1154G>A (OR=2.58, p=0.0035), +460C>T (OR=2.90, p=0.0046), and +405G>C (OR=2.02, p=0.02) have shown susceptible association with AMD. However, VEGF −2578C>A did not show any statistical significance. Further A-A-G-T haplotype comprising of three mutant alleles revealed risk association (OR=12.7, p=0.0030) with AMD. ConclusionThe present study suggests significant genetic associations for VEGF −1154G>A, +460C>T, and +405G>C polymorphisms with AMD. Early detection of individuals with risk to these SNPs could lead to strategies for prevention, early diagnosis, and management of AMD.

The association between vascular endothelial growth factor gene polymorphisms and stroke: a meta-analysis.

ObjectivesNumerous studies have investigated the relationships between vascular endothelial growth factor (VEGF) gene polymorphisms and stroke. However, their findings remain controversial. The objective of this study was to evaluate the relationships between VEGF gene polymorphisms and stroke by a meta‐analysis.Materials and methodsThe PubMed, Embase, China National Knowledge Infrastructure database, Wanfang Chinese database, and VIP Chinese database were systemically searched. Data were extracted by two independent reviewers, and pooled odds ratio (OR) with 95% confidence interval (CI) were calculated.ResultsTen studies were included, including a total of 2331 cases and 1814 controls for +936C>T, 3040 cases and 2649 controls for −1154G>A. Under the dominant and recessive models, respectively, the overall ORs and 95% CIs of +936 T were 1.44, 1.09–1.90, P = 0.01 (1.53, 1.14–2.05, P = 0.005, in Asians) and 1.19, 0.85–1.65, P = 0.31, and the overall ORs and 95% CIs of −1154 A were 0.98, 0.87–1.10, P = 0.75 and 0.95, 0.82–1.11, P = 0.53. No publication bias was found in this meta‐analysis.ConclusionsThe meta‐analysis showed that +936C>T may be a risk factor for stroke, especially in Asians, while −1154G>A was not associated with stroke.

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.

Vascular Endothelial Growth Factor Gene Polymorphisms in Type 2 Diabetes Mellitus; Insertion/Deletion at -2549 is Associated with Retinopathy but not + 405 G/C Polymorphism

Vascular Endothelial Growth Factor Gene Polymorphisms in Type 2 Diabetes Mellitus; Insertion/Deletion at -2549 is Associated with Retinopathy but not + 405 G/C Polymorphism

Vascular endothelial growth factor gene polymorphism is not associated with diabetic retinopathy in Egyptian Patients

Purpose:Vascular endothelial growth factor (VEGF) was implicated as a major contributor to the development of diabetic retinopathy (DR). This study investigated whether single nucleotide polymorphisms of A allele of rs699947 or G allele of rs10434 in the VEGF gene were associated with DR in Egyptian patients with type 2 diabetes mellitus (DM).Methods:This is a case–controlled study which was performed at Cairo University Hospital in 2012 on Egyptian patients with type 2 DM with and without DR. Healthy adults without diabetes comprised the comparison group. Patients underwent an ophthalmological examination and fundus photography. Genotyping was performed for the A allele of rs699947 and the G allele of rs10434 polymorphisms using real-time polymerase chain reaction.Results:A total of 128 patients were enrolled in this study and divided into three groups: Group A included 46 patients with type 2 DM and DR; Group B included 41 patients with type 2 DM without DR; and Group C included 41 healthy controls. There was no significant association between rs699947 or rs10434 and any of the three groups (P = 0.5, P = 0.7, respectively). Allelic frequency in the three groups was not statistically significant for rs699947 or rs10434 (P = 0.6, P = 0.6, respectively).Conclusion:Rs699947 or rs10434 polymorphism was not associated with the presence of DR in Egyptian patients. Further studies are required before genetic testing for polymorphism can be used clinically to correlate with DR.

Association Between Vascular Endothelial Growth Factor Gene Polymorphisms with Breast Cancer Risk in an Iranian Population.

Breast cancer (BC) is one of the most causes of death in women worldwide. It affects Iranian female population approximately a decade earlier than those in other parts of the world. Previous studies have shown that vascular endothelial growth factor (VEGF) gene variants were associated with BC risk. The current study aimed to evaluate the impact of VEGF rs3025039 (+936C>T), rs2010963 (+405C>G), rs833061 (-460T>C), rs699947 (-2578C>A), and rs35569394 (18-bp I/D) polymorphisms on BC risk in an Iranian population in southeast of Iran. This case–control study was done on 250 BC patients and 215 healthy women. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or PCR was used to genotype the polymorphisms. Our findings showed that VEGF rs699947 variant increased the risk of BC (OR = 1.71, 95% CI = 1.15–2.54, P = 0.009, CA vs CC; OR = 2.12, 95% CI = 1.14–3.93, P = 0.021, AA vs CC; OR = 1.78, 95% CI = 1.22–2.60, P = 0.004, CA+AA vs CC; OR = 1.47, 95% CI = 1.12–1.92, P = 0.005, A vs C). The VEGF rs3025039, rs2010963, rs833061, and rs35569394 variants were not associated with risk/protection of BC. In conclusion, our results proposed that VEGF rs699947 polymorphism may increase the risk of BC development. Furthers studies with larger sample sizes and different ethnicities are necessary to confirm our findings.

Vascular endothelial growth factor and hypoxia-inducible factor-1α gene polymorphisms and coronary collateral formation in patients with coronary chronic total occlusions.

Introduction:We evaluated the association between two single nucleotide polymorphisms of the vascular endothelial growth factor gene and one of the hypoxia-inducible factor-1α gene and the degree of coronary collateral formation in patients with a coronary chronic total occlusion.Methods:Totally, 98 patients with symptomatic coronary artery disease and a chronic total occlusion observed during coronary angiography were recruited. Genotyping of two vascular endothelial growth factor promoter single nucleotide polymorphisms (−152G>A and −165C>T) and the C1772T single nucleotide polymorphism of hypoxia-inducible factor-1α were performed using polymerase chain reaction and restriction fragment length polymorphism analysis. The presence and extent of collateral vessel filling was scored by blinded observers using the Rentrop grade.Results:We found no association between the vascular endothelial growth factor −152G>A, −165C>T and hypoxia-inducible factor-1α −1772C>T with the presence and filling of coronary collateral vessels. A history of percutaneous coronary intervention and transient ischaemic attack/cerebrovascular accident were associated with the presence of enhanced collateral vessel formation following binary logistic regression analysis.Conclusion:The study findings suggest that coronary collateral formation is not associated with the tested polymorphic variants of vascular endothelial growth factor and hypoxia-inducible factor-1α in patients with symptomatic coronary artery disease and the presence of a chronic total occlusion.

Association between a vascular endothelial growth factor gene polymorphism (rs2146323) and diabetic retinopathy: a meta-analysis.

BackgroundVascular endothelial growth factor (VEGF) is thought to play an important role in the pathogenesis of diabetic retinopathy (DR). Previous studies have associated the VEGF rs2146323 polymorphism with the risk of DR. However, the results of these studies are inconsistent. A meta-analysis was performed to evaluate the association between the VEGF rs2146323 polymorphism and the risk of DR.MethodsThe PubMed, EMBASE, Web of Science and Google Scholar literature databases until March 2015 were searched. The differences in the studies were expressed in the form of an odds ratio (OR) and the corresponding 95 % confidence interval (CI). Heterogeneity among the studies was tested using the I2 statistic based on the Q test.ResultsA total of four studies (598 cases and 709 controls) were included in the meta-analysis. A significant association was found involving the rs2146323 polymorphism in the dominant model (CA + AA VS. CC) (OR = 1.38, CI = 1.10–1.72, P = 0.005) and the co-dominant model (CA VS. CC) (OR = 1.37, CI = 1.08–1.74, P = 0.008).ConclusionsOur meta-analysis confirmed the association between the VEGF rs2146323 polymorphism and the risk of DR.

The role of NOS2A -954G/C and vascular endothelial growth factor +936C/T polymorphisms in type 2 diabetes mellitus and diabetic nonproliferative retinopathy risk management.

Type 2 diabetes mellitus (T2DM) remains one of the major health problems in Europe. Retinopathy is one of the major causes of morbidity in T2DM, strongly influencing the evolution and prognosis of these patients. In the last 2 decades, several studies have been conducted to identify the possible genetic susceptibility factors involved in the pathogenesis of the disease. However, there is little data related to the involvement of vascular endothelial growth factor (VEGF) and nitric oxide synthase (NOS) gene polymorphisms in the T2DM Caucasian population. The objective of this study was to identify a possible connection between NOS2A −954G/C (rs2297518) and VEGF +936C/T (rs3025039) polymorphisms and the risk of developing T2DM and nonproliferative diabetic retinopathy in a Caucasian population group. We investigated 200 patients diagnosed with T2DM and 208 controls. Genotypes were determined by multiplex polymerase chain reaction-restriction fragment length polymorphism. Statistical and comparative analyses (Fisher’s exact test) for dominant and recessive models of NOS2A −954G/C and VEGF +936C/T polymorphisms revealed an increased risk of T2DM (χ2=8.14, phi =0.141, P=0.004, odds ratio [OR] =2.795, 95% confidence interval [CI] =1.347–5.801; χ2=18.814, phi =0.215, P<0.001, OR =2.59, 95% CI =1.675–4.006, respectively). Also, comparative analysis for the recessive model (using Pearson’s chi-square test [χ2] and the phi coefficient [phi]) reveals that the variant CC genotype of NOS2A gene is more frequently associated with T2DM without retinopathy (χ2=3.835, phi =−0.138, P=0.05, OR =0.447, 95% CI =0.197–1.015). In conclusion, the results of the study place VEGF +936C/T polymorphisms among the genetic risk factor for T2DM, whereas NOS2A −954G/C polymorphisms act like a protective individual factor for nonproliferative retinopathy.

Association between vascular endothelial growth factor gene polymorphisms and the risk of osteonecrosis of the femoral head: Systematic review.

Emerging evidence has shown that vascular endothelial growth factor (VEGF) gene polymorphisms are the key initiators that regulate the expression of the VEGF protein, which has a vital role in osteonecrosis of the femoral head (ONFH). The aim of the present study was to investigate whether polymorphisms of the VEGF genes are associated with the occurrence of ONFH. A comprehensive search was performed on MEDLINE, Embase, Web of Science and China National Knowledge Infrastructure databases before June 2015. Meta-analyses were carried out for the VEGF gene -634G/C polymorphisms (single-nucleotide polymorphism with 3 eligible studies). The pooled odds ratios with 95% confidence intervals (CIs) were used to evaluate the strength of the association. All the eligible studies, involving 1,564 individuals, were identified. According to the inclusion criteria, 3 case-control studies were finally included in the meta-analysis. The present meta-analysis indicates that the VEGF gene -634G/C polymorphism [CC+GC vs. GG: Response rate (RR)=0.79; 95% CI, 0.67-0.92; GG vs. GC: RR=0.83; 95% CI, 0.72-0.97; GG vs. CC: RR=0.82; 95% CI, 0.72-0.93] is associated with the occurrence of ONFH, and the association with the male subgroup (RR=0.78; 95% CI, 0.65-0.94; P=0.009) is more evident. In conclusion, the present meta-analysis suggests that the VEGF gene -634G/C polymorphism has a significant association with ONFH occurrence among the investigated patients (P<0.01).

Abstract 4253: A vascular endothelial growth factor gene polymorphism predicts malignant potential in intraductal papillary mucinous neoplasm

Abstract Background Intraductal papillary mucinous neoplasms (IPMNs) are well known to be premalignant lesions that sequentially progress from adenoma to carcinoma. Radiological type, size of cystic mass, and the presence of mural nodules are widely accepted as predictive malignant factors; however, its underlying mechanism is still unclear. Angiogenesis plays an important role in the progression and metastasis of various tumor types, and vascular endothelial growth factor (VEGF) is a critical component. In previous studies, at least 30 single-nucleotide polymorphisms (SNP) of the VEGF gene have been reported. VEGF +405G/C SNP (rs2010963) is located within the 5′-untranslated region and may affect transcription factor binding affinity. In contrast, VEGF -460C/T SNP (rs833061) is located in the promoter region and may influence promoter activity. Recent studies reported that serum VEGF levels were significantly higher in pancreatic ductal adenocarcinoma (PDAC) patients compared with control subjects, and VEGF +405G/C SNP was strongly associated with the carcinogenesis of PDAC patients. Objective The aim of this study was to investigate the distribution of VEGF SNPs with regard to malignant transformation in IPMN patients. Furthermore, correlations between VEGF SNPs and clinicopathological parameters including the morphological subtypes were statistically analyzed. Methods A total of 169 IPMN and 108 PDAC patients who underwent curative resection were enrolled. Low grade and moderate dysplasia were defined as benign IPMNs, on the other hand, high grade dysplasia and invasive carcinoma were defined as malignant IPMNs. The intraductal components were classified into four distinct epithelial subtypes, gastric, intestinal, pancreatobiliary, and oncocytic, based on their epithelial morphology on hematoxylin and eosin staining. VEGF +405G/C and -460C/T polymorphisms were examined by TaqMan Allele Discrimination. Results VEGF +405C/C was found more frequently in malignant IPMNs compared with +405G/G (odds ratio: 2.7, P = 0.04), and +405C allele was associated with malignant IPMNs compared with +405G (P = 0.055). In branch duct IPMNs, VEGF +405C/C was significantly associated with malignant transformation (CC vs GG; odds ratio: 4.0, P = 0.03, CC vs CG+GG; odds ratio: 3.3, P = 0.04), and there was a trend of VEGF +405C/C associated with malignant transformation of gastric type IPMNs (CC vs GG; odds ratio: 3.0, P = 0.07). When the survival outcomes were analyzed based on VEGF +405G/C SNPs, however, there was no relationship between VEGF SNPs and overall survival in patients with both IPMNs and PDAC. Conclusion VEGF +405G/C SNP was significantly associated with malignant transformation in IPMNs, especially branch duct and gastric type IPMNs. VEGF +405G/C SNP might be helpful in predicting clinical course in pancreatic disease with potential for malignant transformation. Citation Format: Suguru Yamada, Norimitsu Yabusaki, Tsutomu Fujii, Mitsuro Kanda, Hiroyuki Sugimoto, Yasuhiro Kodera. A vascular endothelial growth factor gene polymorphism predicts malignant potential in intraductal papillary mucinous neoplasm. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4253. doi:10.1158/1538-7445.AM2015-4253

Association of vascular endothelial growth factor gene polymorphism with diabetic retinopathy in different population: a meta-analysis

Objective To assess the association of vascular endothelial growth factor (VEGF) gene-460C/T and -634C/G polymorphism with diabetic retinopathy (DR) among patients in Asia and European by meta-analysis. Methods A systematic search of electronic databases (PubMed, Cochrane Library, EMBASE, VIP, Wanfang technological, CNKI, etc.) was carried out until Jun, 2014. Case-control studies on the relationship between genetic polymorphism of VEGF-460C/T and VEGF-634C/G with diabetic retinopathy were included in this analysis. The data were quantitatively analyzed by RevMan 5.0 software after assessing the quality of included studies. The pooled odds ratios (OR) and their corresponding 95% confidence intervals (CI) were used to assess the strength of the association. Results VEGF-460C/T (7 studies: 899 cases and 786 controls) and VEGF-634C/G (10 studies: 1615 cases and 1861 controls) were inclued in this meta-analysis. Significant association was found for -460C/T polymorphism in Aisa (C versus T: OR=1.52, 95%CI was [1.22, 1.90], Z=3.72, P=0.0002; CC versus CT+ TT: OR=1.61, 95%CI was [1.19, 2.19], Z=3.05, P=0.002; TT versus CT+ CC: OR=0.64, 95%CI was [0.41, 0.98], Z=2.07, P=0.04), and VEGF-634CC gene type was associated with DR in European (OR=1.56, 95%CI[1.08, 2.25], Z=2.37, P=0.02). No significant publication bias was found. Conclusions The meta-analysis demonstrated that DR was associated with VEGF-460C/T polymorphism in Asia, and C alleles and CC gene type was the risk polymorphism; VEGF-634C/G polymorphism was not associated with DR, but its CC genotype maybe the risk factor in European. Further case-control studies based on larger sample size are still needed, especially for -634C/G polymorphism. Key words: Diabetic retinopathy/etiology; Genetic pleiotropy; Vascular endothelial growth Factors; Meta-analysis

Vascular endothelial growth factor gene polymorphisms and psoriasis susceptibility: a meta-analysis.

The aim of this study was to explore whether vascular endothelial growth factor (VEGF) polymorphisms confer susceptibility to psoriasis. Meta-analyses were conducted to examine the associations between the +405 C/G, -460 C/T, -1154 A/G, and -2578 A/C polymorphisms of VEGF and psoriasis using allele contrast and recessive, dominant, and additive models. Seven studies on VEGF polymorphisms and psoriasis involving 1956 subjects (psoriasis patients 665, controls 1291) were included in this meta-analysis. We observed no association between psoriasis and the VEGF +405 C allele in all study subjects (odds ratio = 0.984, 95% confidence interval = 0.754-1.285, P = 0.906), but stratification by ethnicity indicated a significant association between the VEGF +405 C allele and psoriasis in Asians (odds ratio = 0.762, 95% confidence interval = 0.628-0.923, P = 0.005). In addition, we observed a significant association between the VEGF -460 C allele and psoriasis in Europeans (odds ratio = 0.807, 95% confidence interval = 0.672-0.968, P = 0.021). Meta-analyses of the -1154 A/G polymorphism also revealed a significant association with psoriasis in Europeans. However, the VEGF -2578 A/C polymorphism showed no association in all subjects or in Europeans or Asians. This meta-analysis suggests the VEGF +405 C/G polymorphism confers susceptibility to psoriasis in Asians, and that the -460 C/T and -1154 A/G polymorphisms confer susceptibility to psoriasis in Europeans.

Vascular endothelial growth factor -634 G/C polymorphism and risk of cancer: an updated meta-analysis

The association between vascular endothelial growth factor (VEGF) gene polymorphisms and risk of cancer has been investigated in several studies published previously; however, the individual results are inconclusive. Therefore, we performed a meta-analysis to establish evidence for an association between the VEGF -634 G/C polymorphism and risk of cancer. We searched PubMed, Medline, and Korean Studies Information Service System databases and identified 29 case-control studies, containing data of 25,324 individuals, for this meta-analysis. The odds ratio (OR) and 95% confidence interval (95%CI) were used to determine the strength of the association. Overall, no significant association was detected in the allele model (G allele vs C allele, OR = 0.98, 95%CI = 0.93-1.03), dominant model (G/G+G/C vs C/C, OR = 1.00, 95%CI = 0.90-1.11), or recessive model (G/G vs G/C+C/C, OR = 0.96, 95%CI = 0.89-1.03). The meta-analysis results suggest that the VEGF -634 G/C polymorphism may not be related to the development of cancer. However, additional studies with larger sample size are required in order to provide supporting evidence.

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.

Vascular endothelial growth factor gene polymorphisms in age-related macular degeneration in a Turkish population.

To assess the association between age-related macular degeneration (AMD) and three single nucleotide polymorphisms (SNPs) related to the vascular endothelial growth factor (VEGF) gene. The patients who were diagnosed with AMD were included in this prospective study. Three SNPs (rs1413711, rs2146323, and rs3025033) of the VEGF gene were genotyped by real-time polymerase chain reaction in the genomic DNA isolated from peripheral blood samples of the 82 patients and 80 controls. The genotype frequencies of rs1413711 and rs2146323 were not significantly different between the study group and the control group (P=0.072 and P=0.058). However, there was a significant difference in the genotype frequencies of these SNPs between the wet type AMD and dry type AMD (P=0.005 and P=0.010, respectively). One of the SNPs (rs1413711) was also found to be associated with the severity of AMD (P=0.001) with significant genotype distribution between early, intermediate, and advanced stages of the disease. The ancestral alleles were protective for both SNPs while the polymorphic alleles increased the risk for dry AMD. VEGF SNPs rs1413711 and rs2146323 polymorphisms are significantly associated with AMD subtypes in our population.

Vascular endothelial growth factor (VEGF) gene polymorphisms and breast cancer risk in Punjabi population from North West India

The purpose of this study was to evaluate the association of seven VEGF promoter polymorphisms with breast cancer risk in Punjabi population from North West India. We screened DNA samples of 102 sporadic breast cancer patients and 102 unrelated healthy, gender, and age-matched individuals for seven VEGF promoter polymorphisms [-417 C/T (rs833062), -172 C/A (rs59260042), -165 C/T (rs79469752), -160 C/T, -152 G/A (rs13207351), -141 A/C (rs28357093) and -116 G/A (rs1570360)] by direct sequencing. The frequency of GG, GA, and AA genotype of -152 G/A polymorphism was 26.47 vs 38.34%, 46.08 vs 51.96%, and 27.45 vs 9.80%, in patients and controls, respectively. VEGF -152 AA genotype was significantly associated with increased risk for breast cancer (OR = 4.04, 95%CI, 1.69-9.68, p = 0.001; recessive model OR = 3.48, 95%CI, 1.59-7.63, p = 0.001). For VEGF -116 G/A polymorphism, G and A allele frequencies were 65.2 vs 76.47% and 34.8 vs 23.53% in patients and controls, respectively. Individuals having -116 AA genotype (OR = 3.40; 95%CI, 1.24-9.37; p = 0.014) and A allele (OR = 1.73; 95%CI, 1.12-2.67; p = 0.012) were associated with increased risk for breast cancer. VEGF -165 C/T and -141 A/C polymorphisms were associated with reduced risk for breast cancer. There was significantly decreased frequency of CT genotype (4.90 vs 18.63%; p = 0.002) and T allele (2.45 vs 9.31%; p = 0.003) of -165 C/T polymorphism among breast cancer patients as compared to controls. VEGF -141 A and C allele frequency were 96.57 vs 91.18% and 3.43 vs 8.82% in patients and controls, respectively. Significant reduced risk for breast cancer was observed with AC genotype (OR = 0.34, 95%CI, 0.14-0.86; p = 0.019) and C allele (OR = 0.37; 95%CI, 0.15-0.89; p = 0.023) of -141 A/C polymorphism. We did not observe association of VEGF -417 T/C, -172 C/A, -160 C/T polymorphisms with breast cancer risk in the studied subjects (p > 0.05). The VEGF -152 G/A and -116 G/A polymorphisms were found to be significantly associated with increased risk for breast cancer while -165 C/T and -141 A/C polymorphisms were found to be associated with decreased risk for breast cancer in Punjabi population from North West India.

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.