Endothelial Growth Factor Gene Polymorphisms Research Articles

VEGF gene sequence variation defines VEGF gene expression status and angiogenic activity in non-small cell lung cancer

Different vascular endothelial growth factor (VEGF) gene polymorphisms have been shown to result in different VEGF gene responsiveness to various stimuli and different capacity for VEGF protein production. In the present study, we examined four VEGF gene polymorphisms in thirty–six individuals with non-small cell lung cancer (NSCLC). Gene polymorphisms were correlated with the VEGF protein expression in cancer cells and the tumor angiogenic activity. The −2578C/C, −634G/G and −1154A/A and G/A alleles in the VEGF gene were linked with low VEGF expression, while the −2578C/A, the −634 G/C and the −1154G/G alleles were linked with high VEGF expression. Tumors with −2578C/C had a significantly lower vascular density (VD) compared to the −2578C C/A. Similarly, cases with the −634G/G VEGF polymorphism had a singinificanltly lower vascular density compared to the combined C/C and G/C groups. In addition, the −1154A/A polymorphism seemed to relate with poor vaccularization but the difference did not reach significance. It is concluded that inherited VEGF sequence variations, which characterize the tumor genome itself, are strong determinants of the molecular VEGF and VEGF-downstream phenotype of NSCLC. The large variation in angiogenicity between tumors of similar histologic morphology emerges as a consequence of the ‘parental’ VEGF gene ability to produce VEGF.

Vascular endothelial growth factor gene polymorphisms and pre-eclampsia.

Vascular endothelial growth factor (VEGF) plays a crucial role in physiological vasculogenesis and vascular permeability and has been implicated in the pathogenesis of pre-eclampsia. Our present study was undertaken to identify associations between three functional VEGF gene polymorphisms, linked with altered VEGF gene responsiveness, and pre-eclampsia. The study involved 42 pre-eclamptic and 73 healthy control women who were genotyped for the -2578C/A, -634G/C and 936C/T polymorphisms of the VEGF gene. No significant association between genotypic or allelic frequencies in women with pre-eclampsia relative to controls was found. A statistically significant difference was found for allelic frequencies of the 936C/T polymorphism between women with severe pre-eclampsia and controls (odds ratio: 2.70; 95% confidence interval: 1.09-6.63; P = 0.019). VEGF gene polymorphisms studied are unlikely to be major predisposing factors for pre-eclampsia. The presence of the 936T allele probably has a considerable effect on disease modification.

Vascular endothelial growth factor gene polymorphism are associated with allograft coronary artery disease after clinical heart transplantation

Statement of purpose: Cardiac allograft arteriosclerosis is a complex process of alloimmune response, chronic inflammation and smooth muscle cell proliferation. It is a major cause of morbidity and mortality after orthotopic heart transplantation (HTx). Vascular Endothelial Growth Factor (VEGF) is a mitogen for endothelial cells and is expressed by myocardial tissue and T-cells. VEGF induces migration and proliferation of endothelial cells and stimulates production of thrombogenic protein tissue factor in endothelial cell and monocytes. This study investigates whether genetically determined variation in VEGF expression influences the development of allograft coronary artery disease (CAD) after clinical HTx.

Vascular endothelial growth factor gene polymorphism is associated with calcium oxalate stone disease.

Growth factor-related genes regulate cell growth, differentiation and apoptosis in the kidney in response to cellular injury. One of the theories of stone formation is that cellular injury, and thus growth factors, play a role. We therefore investigated the association between growth factor genes and calcium oxalate stone disease. The most frequently seen polymorphism of the vascular endothelial growth factor (VEGF) gene is Bst U I C/T, which is located upstream at the -460th nucleotide. Other growth factor-related gene polymorphisms include the cytochrome P450c17alpha enzyme (CYP17) gene MspA I C/T polymorphism at the 5'-UTR promoter region, the epidermal growth factor receptor (EGFR) gene Bsr I polymorphism (A to T) at position 2,073, and the insulin-like growth factor-2 (IGF-2) gene Apa I A/G at exon 9. All four polymorphisms were used as genetic markers in this study in the search for an association between stone disease and growth factor related genes. A normal control group of 230 healthy people, and 230 patients with calcium oxalate stone, were examined. The polymorphism was seen following polymerase chain reaction based restriction analysis. The result revealed a significant difference between normal individuals and stone patients (P=0.0003, Fisher's exact test) in the distribution of the VEGF gene polymorphism as well as an odds ratio of 1.30 (95% confidence interval=0.993-1.715) per copy of the "T" allele. Whereas, the IGF-2, EGFR and CYP17 gene polymorphisms did not reveal a significant association with stone disease. We conclude that the VEGF gene Bst U I polymorphism is a suitable genetic marker of urolithiasis.

Steroid-sensitive nephrotic syndrome and vascular endothelial growth factor gene polymorphisms.

Genetic polymorphisms have been recognized as important determinants of gene expression. Three common single nucleotide polymorphisms have been identified in the promoter and 5' untranslated region of the vascular endothelial growth factor (VEGF) gene: -460 C --> T, -141 A --> C and +405 G --> C. As VEGF has been postulated to play a role in the pathogenesis of childhood steroid-sensitive nephrotic syndrome (SSNS), this study tested the hypothesis that VEGF genotype may be associated with susceptibility to SSNS. We examined the genotype frequencies of these polymorphisms in a total of 116 children with SSNS and 150 control subjects, using polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP). There were no statistically significant differences in any of the genotype frequencies between SSNS patients and controls. We conclude that VEGF -460, -141 and +405 genotypes are not associated with susceptibility to childhood SSNS.

Vascular endothelial growth factor gene polymorphism are associated with acute rejection after heart transplantation

Lambda) for the detection of HLAab in serum/plasma of 54 patients. 10/54 patients exhibited a positive ELISA post-LTx (ELISA ). 9 ELISA patients were in the ACSAgroup and one patient with preformed donor-specific HLAab received ACSA for 4 months. The HLAab pattern was: 2 patients had both class I and II HLAab, 3 class II and 5 class I. 2/10 of these patients tested ELISA pre-LTx. In 6/9 patients we were able to identify donor-specific HLAab. De novo HLAab were developed in 5/10 ELISA patients. In 9/10 of ELISA patients, the presence of HLAab was associated with a P/R during the first 18 months, comparatively with only 2/14 in the ELISA-/ACSA group (p 0.0003) and with 13/30 in ELISA-/ACSA(p 0.01). There was a tendency for fewer P/R in ACSA /ELISArelative to ACSA-/ ELISApatients (p 0.08). The frequency of HACR episodes in ELISA group was significantly higher than in ELISAgroup (28/83 versus 36/340, 2 27.84, p 0.00001). Furthermore, the ELISA patients required increased immunosuppression ( 2 course of bolus steroids and/or antilymphocytic agents-p 0.005). Conclusions: The presence of ELISA-detected HLAab positively correlated with increased risk of severe acute rejection. These LTx patients may benefit from an altered strategy of immunosuppression. LTx recipients in the ACSA protocol exhibited the lowest prevalence of P/R.

Vascular endothelial growth factor gene polymorphisms are associated with acute renal allograft rejection.

Acute rejection is a major cause of reduced survival of renal allografts. Vascular endothelial growth factor (VEGF) is a mitogen for endothelial cells and is expressed widely by renal tissue and T cells. VEGF influences adhesion and migration of leukocytes across the endothelium. This study investigates whether genetically determined variation in VEGF expression influences the development of renal allograft rejection. VEGF promoter polymorphisms were examined by using sequence-specific primer-PCR in 173 renal transplant recipients. Acute rejection occurred in 38.7%; median time to first rejection episode was 14 d. VEGF in vitro expression was investigated in stimulated leukocytes from 30 controls. The -1154*G and -2578*C alleles were associated with higher VEGF production. VEGF -1154 GG and GA genotypes were significantly associated with acute rejection risk at 3 mo (P = 0.004, odds ration [OR] = 6.8, 95% CI = 1.8 to 25 and P = 0.035, OR = 4.1, 95% CI = 1.1 to 15, respectively). Furthermore, VEGF -2578 CC and CA genotypes were associated with increased rejection risk (P = 0.005, OR = 4.1, 95% CI = 1.5 to 11.3 and P = 0.035, OR = 2.7, 95% CI = 1.1 to 7, respectively). These polymorphisms demonstrate linkage disequilibrium (P = 0.001). These data indicate that the -1154*G and -2578*C containing genotypes, encoding higher VEGF production, are strongly associated with acute rejection and may be useful markers of rejection risk.

Vascular Endothelial Growth Factor Gene Polymorphisms in Women who Experienced Repeated Pregnancy Losses

The well accepted causes of pregnancy loss are chromosomal anomalies, uterine anomalies, thrombophilic and immune disorders and endocrine dysfunction. During early gestation, VEGF is essential for the maturation of oocytes, the proliferation of trophoblasts, the implantation and development of the embryo, the angiogenesis of the placenta, and the growth of maternal and fetal blood vessels in the uterus. The aim of this study is to establish the incidence of -634G/C VEGF polymorphism in our study lot that included women with recurrent miscarriages as well a comparation with the incidence of the same polymorphism in a control lot of subjects with no reproduction faillure history. The study lot included 35 women with multiple pregnancies losses, aged between 18 and 41 years old. The control lot consists of 59 healthy individuals that had no experience of reproductive failure. Genotyping of -634G/C VEGF was done for both study and control lots. We found a significant statistic difference of the alleles frequencies between the two tested cohorts, the study lot and the control lot. Further studies should focus on testing VEGF variants in women that experience repeated pregnancy losses in order to establish an association among VEGF polymorphisms, endometrial VEGF expression and plasma VEGF levels in RPL patients.