VEGF Genotypes Research Articles

VEGF Genotype and Allele Frequency of Diabetes Mellitus and Diabetic retinopathy in Lahore, Pakistan

Diabetic retinopathy is characterized as basement membrane (BM) thickening, pericyte loss, endothelial cell (EC) dysfunction, microaneurysms, microvascular infarcts and neovascularization in a patient with diabetic retinopathy. Objectives: To determine the VEGF genotype and allele frequency of diabetes mellitus and diabetic retinopathy in Lahore, Pakistan. Methods: A total of 100 blood samples were taken including diabetes mellitus (50) and diabetic retinopathy patients (50). Diseased and control subjects were selected for blood sampling. Demographic and clinical characteristics was evaluated. The BMI, HbA1c and the blood pressure of both groups were also examined. The VEGF genotype and allele frequency of diabetes mellitus and diabetic retinopathy was done. The statistical analysis was done by chi-square test and SPSS to study significant differences in control and diabetic retinopathy subjects. Results: The normal estimation of DM group was 46.18 ± 1.23 years while of DR class was 52.86 ± 1.36 years. The mean value of BMI of DM group was 26.0±0.62 while of DR group was 26.57±0.70.
 DD genetic mutation was substantially higher in diabetic retinopathy bunch (p<0.05) relative to the II gene mutation, the huge contrasts (p<0.05) were seen in diabetic group. Conclusions: This study concluded that Vascular endothelial growth factor gene was detected in both group of diabetes. In retinopathy people with T2DM the substantial elevated VEGF DD genetic variation was seen relative to retinopathy people without diabetes.

VEGF gene polymorphism in complicated infective endocarditis

Introduction. Infective endocarditis (IE) is a bacterial disease with frequent pathogen localization on the heart valve apparatus. IE is characterized by rapid development of heart failure and frequent thromboembolic complications (TEC). IE features are accounted for by foreign pathogen nature and state of human immune system (IS). The imbalanced IS in infective endocarditis is manifested by impaired cytokine-mediated interactions. This confirms the rationality of studying cytokines to advance understanding of the pathogenesis for various conditions. Most cytokine genes are characterized by polymorphism and existing isoforms underlying disease predisposition. Genetic polymorphism of vascular endothelial growth factor A (VEGF-A) plays an important role in the induction of vasculogenesis and angiogenesis. The pathogenetic VEGF role in IE has not been thoroughly studied. Research objective analysis of polymorphic nucleotide sequence variants in the vascular endothelial growth factor gene, taking into account a relation with its serum concentration in patients with infective endocarditis. Materials and methods. 86 patients treated with verified diagnosis of infective endocarditis at the Scientific Research Institute Regional Clinical Hospital No. 1 of Krasnodar were divided into two clinical groups in accordance with the IE course: Group 1 IE with TEC (n = 44), group 2 IE without TEC (n = 42), and the control group consisted of 20 apparently healthy individuals. The concentration of serum VEGF-A (pg/mL) was measured by ELISA on day 1 of hospitalization. Genomic DNA was isolated from whole blood leukocytes and used to determine the frequency of genotypes of VEGF gene polymorphic variants. Results. Significant differences in the frequency distribution of VEGF-rs2010963 genotypes between patients with infective endocarditis and control group were revealed: G/G (OR = 0.25; p = 0.012) and G/C (OR = 4.28; p = 0.022), as well as differences between VEGF concentrations for various SNP-rs2010963 genotypes (p = 0.0001). A study of VEGF genotype frequency distribution between patients of clinical groups showed a significantly decreased frequency of the genotype G/G (rs2010963) in the IE group with TEC (OR = 0.21; p = 0.014) and increased frequency of G/C (OR = 4.72; p = 0.024) compared with the control group, whereas in patients with IE without TEC, significant (p = 0.0003) differences in serum concentrations of VEGF-rs2010963 were found in accordance with genotypes GG/CC (p = 0.01) and GG/GC (p = 0.003). Conclusion. The relationship between the VEGF genotypes (G/G and G/C of rs2010963 polymorphism) and related serum concentration among patients with IE was revealed. Carriers of the minor C allele (rs2010963) had higher serum VEGF levels. The results obtained complement and systematize current scientific data on the disease pathogenesis, as well as focus on the genetic determinant of the developing complications.

Blood Glucose, HbA1c Level, and its Correlation with VEGF-A (+405G/C) Polymorphism as Biomarker Predicts the Risk of Retinopathy and Nephropathy in Type 2 Diabetic Patients.

Diabetes-related vascular complications linked to increase in the expression of VEGF and its receptors. It helps to accelerate tissue damage inflicted by hyperglycemia, which is potential risk for diabetic complications. The study aimed to assess VEGF genetic polymorphism and its correlation with glucose and HbA1C level among Sudanese patients with diabetic retinopathy and nephropathy. A case-control study was conducted among a total of 252 subjects and divided into four groups of 63 subjects each. Glucose and HBA1c were measured then the VEGF gene was amplified using polymerase chain reaction. The data were analyzed using SPSS. The HBA1c, and blood glucose levels had significantly (P value≤0.00001) highest mean in the DR group, DN group followed by DM. There is a non-significant correlation between VEGF Genotypes and HbA1c, and blood glucose levels (P value≤0.102, 0.173) Patients with GC genotypes will be 74.6%, and 54% higher at risk to develop DR, and DN respectively and 40 % lower at risk to develop DM than those without GC genotype. While patients with CC genotypes will be 22.2% higher at risk of developing DM and 9.5%, 12.2% higher at risk of developing DR and DN respectively. The VEGF +405G/C gene polymorphism is linked to diabetic retinopathy, and diabetic nephropathy in type 2 Sudanese diabetics, and the presence of the GC genotypes and G allele is a significant predictor for retinopathy. There is no significant relation between HbA1C serum levels, blood glucose, and the VEGF +405G/C gene polymorphism.

Association of Different Genotypes of VEGF Gene with Changes in Aerobic Capacity Following Endurance Training in Obese Women

Objective: Obesity is a chronic disease characterized by an excessive mass of adipose tissue in the body. The present study aimed to investigate the relationship between different genotypes of VEGF gene and changes in aerobic capacity following aerobic exercise in obese women. Materials and Methods: In this study, 23 inactive women aged 34 to 43 years with BMI 30 and 35 were purposefully selected and participated in eight weeks of aerobic exercise including 4 sessions per week and 30 minutes per session with an intensity of 55 to 75% of maximum heart rate. Before and after the training period, aerobic power (VO2max) was measured by the modified Bruce test. Saliva Sample was collected at 12 hours of fasting to measure VEGF genotypes. To compare aerobic capacity between different genotypes, since we had three genotypes GG, CG, and CC, one-way analysis of variance was used. Results: Although the mean amount of aerobic power changes of GG genotype was somewhat higher after eight weeks of aerobic training than the other two genotypes, this difference was not significant. (P-value= 0.663, P-value= 0.873 and P-value= 0.173, respectively). Conclusion: Eight weeks of aerobic training leads to increased aerobic capacity in obese women and increased VEGF plays a role, but there is not seemingly a difference between different VEGF genotypes for these changes. In any case, since this study was conducted for the first time, we need more studies to draw a more accurate conclusion.

Association between VEGF -2578 C> A Polymorphism with VEGF Serum Levels in Gastritis with Helicobacter Pylori

Mucosal damage in people with gastritis causes the production of VEGF. VEGF is a neoangiogenesis function to repair damaged tissue. Excess production can cause cancer risk. VEGF genotype polymorphisms are thought to affect the production of serum VEGF levels. The aim of this study was to determine the relationship between VEGF - 2578 C> A polymorphism and serum VEGF levels in H. pylori gastritis. Method: cross-sectional study was conducted at H. Adam Malik General Hospital and Network Hospital with 100 samples. Endoscopic examination was performed to assess the gastric mucosa and a tissue biopsy was performed. The urea breath test (UBT) test and the Campylobacter like organism (CLO) test to determine H. pylori infection. VEGF - 2578 C> A was checked by Polymerase Chain Reaction (PCR). The data will be analyzed by univariate and bivariate. Result: One hundred people with gastritis, of which 59 people were infected with H. pylori. In this study, H. pylori infection did not have a significant relationship with VEGF levels. VEGF - 2578 C> A polymorphisms also had no relationship to serum VEGF levels. Conclusion: There is no correlation between VEGF - 2578 C> A polymorphism with VEGF serum levels (p> 0.05). Keywords: VEGF polymorphisms, VEGF - 2578 CA, H. pylori, Gastritis.

Association of VEGF and p53 Polymorphisms and Spiral Artery Remodeling in Recurrent Pregnancy Loss: A Systematic Review and Meta-Analysis.

Many studies have reported the association of VEGF-1154G/A, VEGF 936C/T, and p53 Arg72Pro polymorphisms with recurrent pregnancy loss (RPL), but the outcomes are inconsistent. We have used a meta-analysis to associate these polymorphisms with RPL, having the spiral artery remodeling as a major risk factor. The studies were identified from three different reputed databases, namely ScienceDirect, PubMed/Medline, and Scopus. The eligible studies of VEGF-1154G/A, VEGF 936C/T, and p53Arg72Pro polymorphisms associated with the RPL were selected for the analysis. They were segregated into three different ethnic groups as Asians, Caucasians, and mixed population. For the analysis, the overall prevalence, odds ratio, risk ratio, relative risk ratio, and p-values were calculated. A total of 3,241 RPL cases and 3,205 healthy controls from 21 different case-control studies were analyzed. RPL was highly prevalent in the mixed population with VEGF-1154G/A and p53 Arg72Pro polymorphisms (70.04 and 66.46%, respectively) and in the Asian population with VEGF 936C/T polymorphism (53.58%). The homozygous recessive genotypes of VEGF and p53 exhibited significant association between the respective polymorphisms and RPL along with the increased risk of outcome. The current analysis conclusively reports the geographic distribution of the different genetic polymorphisms which shows high association with the progression of RPL. Understanding the spectrum of polymorphisms on different populations with the spiral artery remodeling as a risk factor encloses the importance of the vasculature during the pregnancy.

Role of VEGF Polymorphisms in the Susceptibility and Severity of Interstitial Lung Disease.

The search for biomarkers that can help to establish an early diagnosis and prognosis of interstitial lung disease (ILD) is of potential interest. VEGF polymorphisms have been implicated in the development of several lung disorders. Consequently, we assessed, for the first time, the role of VEGF polymorphisms in the susceptibility and severity of ILD. A total of 436 Caucasian ILD patients (244 with idiopathic interstitial pneumonias (IIPs) and 192 with non-IIP) and 536 ethnically-matched healthy controls were genotyped for VEGF rs833061, rs1570360, rs2010963, rs3025020, and rs3025039 polymorphisms by TaqMan assays. Pulmonary function tests were collected from all the patients. VEGF serum levels were determined by ELISA in a subgroup of patients. No VEGF genotype, allele, carrier, or haplotype differences were found between ILD patients and controls as well as between IIP and non-IIP patients. However, an association of rs1570360 with IIP in women and also with lung function in IIP patients was found. None of the VEGF polymorphisms were associated with VEGF levels. In conclusion, our results suggest that VEGF does not seem to play a relevant role in ILD, although rs1570360 may influence the severity of ILD in women and a worse outcome in IIP patients.

Phase II trial of carboplatin and bevacizumab in patients with breast cancer brain metastases

BackgroundWe aimed to examine the safety and efficacy of bevacizumab and carboplatin in patients with breast cancer brain metastases.MethodsWe enrolled patients with breast cancer and > 1 measurable new or progressive brain metastasis. Patients received bevacizumab 15 mg/kg intravenously (IV) on cycle 1 day 1 and carboplatin IV AUC = 5 on cycle 1 day 8. Patients with HER2-positive disease also received trastuzumab. In subsequent cycles, all drugs were administered on day 1 of each cycle. Contrast-enhanced brain MRI was performed at baseline, 24–96 h after the first bevacizumab dose (day + 1), and every 2 cycles. The primary endpoint was objective response rate in the central nervous system (CNS ORR) by composite criteria. Associations between germline VEGF single nucleotide polymorphisms (rs699947, rs2019063, rs1570360, rs833061) and progression-free survival (PFS) and overall survival (OS) were explored, as were associations between early (day + 1) MRI changes and outcomes.ResultsThirty-eight patients were enrolled (29 HER2-positive, 9 HER2-negative); all were evaluable for response. The CNS ORR was 63% (95% CI, 46–78). Median PFS was 5.62 months and median OS was 14.10 months. As compared with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, patients with ECOG PS 1–2 had significantly worse PFS and OS (all P < 0.01). No significant associations between VEGF genotypes or early MRI changes and clinical outcomes were observed.ConclusionsThe combination of bevacizumab and carboplatin results in a high rate of durable objective response in patients with brain metastases from breast cancer. This regimen warrants further investigation.Trial registrationNCT01004172. Registered 28 October 2009.

Clinical and genetic features of the formation of concomitant visceral pathology in workers with industrial fluorosis

Introduction. The urgency of the problem determines the high level of occupational morbidity in aluminum production workers and the prevalence of somatic pathology, which occupies one of the leading positions in the pathogenesis of fluorosis.The aim of the study is to determine the clinical and genetic features of the nature of concomitant visceral pathology in workers with industrial fluorosis.Materials and methods. A complex of clinical, biochemical, molecular, genetic, and instrumental research methods was used in patients with fluorosis (246 people) and in the control group (106 people).Results. A high frequency of health disorders in workers engaged in the production of aluminum was determined during long-term monitoring. An extended clinical and genetic study of the state of somatic organs in workers with fluorosis and in control is presented. It is revealed that in the group of subjects with proven diagnosis, pathologies concomitant with the main disease were significantly more common: pathologies of musculoskeletal and articular systems, blood circulation, respiratory (rhinitis, chronic, toxic and dust-borne bronchitis, chronic obstructive pulmonary disease), hepatobiliary (steatosis, fluoride hepatopathy), gastrointestinal tract (chronic gastritis, cholecystopancreatitis), renal systems (pyelonephritis, urolithiasis), as well as a combination of several nosologies was in 43%. The association of GG VEGF genotypes with chronic pyelonephritis and TT Il1ß, GSTT 1 0/0 with fluoride hepatosis was revealed in patients with fluorosis.Conclusions. The structure of occupational morbidity in workers of the main professions of aluminum production is dominated by concomitant pathology of functional systems against the background of bone destruction, determined by endogenous factors of the course of metabolic processes of the body.The authors declare no conflict of interests.

Vascular endothelial growth factor C/A 2578 gene polymorphism and umbilical artery Doppler in preeclamptic women

Preeclampsia is strongly associated with placental hypoperfusion. Genetic factors have an impact on the pathogenesis of preeclampsia. The aim is to assess the association of Vascular Endothelial Growth Factor (C2578A) gene polymorphism with the occurrence and severity of preeclampsia and the umbilical artery Doppler changes among preeclamptic women. This case-control study was conducted in clinical and Chemical pathology and Obstetrics departments in Beni- Suef University, Egypt. Two hundred and ninety pregnant women above 20 weeks gestational age until delivery were divided into 2 main groups. The patient group included 145 preeclamptic women who were further sub grouped according to the severity of preeclampsia into 82 severe and 63 mild cases. Control group included 145 normotensive pregnant women. Our primary outcome was detection of VEGF C 2578 A gene mutations by a polymerase chain reaction. A secondary outcome was Doppler changes in the pulsatility index of the umbilical artery compared with VEGF genotypes. Our study showed that VEGF C 2578 A genotype and alleles frequencies were not related to the occurrence of preeclampsia (p-value 0.513 and 0.549, respectively), odds ratio (95%CI) 1.154 (0.724-1.848). Mild preeclamptic cases showed no significance comparing VEGF genotypes studied and pulsatility index of the umbilical artery. However, severe cases showed p-value < 0.0001. We concluded that VEGF 2578C/A polymorphism had no association with the occurrence of preeclampsia in studied groups, whereas there was a significant relationship among severe cases between CA and CC genotypes and pulsatility index of the umbilical artery.

Clinical and experimental studies of bone tissue in fl uorosis

Introduction. Despite the signifi cant reduction in the production of electrolytic aluminum, the frequency of fl uorosis is a leader in this industry. In this pathology, fi rst of all, bone tissue actively reacts to the impact of factors of the working environment. The aim of the study was to study the eff ect of chronic fl uoride intoxication on the morphofunctional state of bone tissue. Materials and methods. Th e analysis of bone mineral density, structural rearrangement of skeletal bones was evaluated by x-ray method using photon densitometry. Biochemical status of blood of workers with fl uorosis included determination of parameters of mineral homeostasis (level of calcium, phosphorus) and genetic markers (COL1A1, IL1β, IL6, VEGF). Histological analysis of bone tissue was carried out in an experiment on white rats.Results. A comprehensive clinical and experimental study of bone tissue under chronic fl uoride intoxication is presented. A signifi cant correlation of GG COL1A1, TT IL1β, GC IL6, GC VEGF genotypes with the development of osteosclerosis was revealed. Th e study showed the relationship of combined signs of fl uorosis, confi rmed by experimental data on persistent bone destruction.Conclusions. Th e leading clinical and radiological syndrome of industrial fl uorosis is the defeat of the musculoskeletal system against the background of gross violations of the morphological and functional structure of the bones of the skeleton, due to the osteotropic mechanism of action of fl uorides and the genetic status of the body.

Genotypes of the genes of vegf, tnf-a and tnf-b in patients with bladder cancer in the t1n0m0 stage and their association with the degree of neoplasia of the tumor

36 patients with bladder cancer in the T1N0M0 stage were selected in the study Of the 36 patients, there were 20 men and 16 women. The age of men was 57.1±5.0, women 54.2± 5.1 years. Thirty healthy individuals constituted a control group, gender characteristics and age consistent with those of patients with bladder cancer. 36 patients with RSM G1 were diagnosed in 2 patients, G2 in 30 patients, G3 in 4 patients. The ratio of GG / GC / CC GEG / GC / CC gene of VEGF patients to the C-r bladder in the T1 stage was 46.7% / 40.1% / 13.3%, in the group of healthy subjects 43.3% / 46.7% / 10%. The ratio of the genotypes of the GC / GA / AA gene of TNF-a to patients with C-r bladder in the T1 stage is 43.75% / 56.25% / 0% in the group of healthy subjects, 43.3% / 46% / 10%. The ratio of TT / TC / SS genotypes of the TNF-b gene in patients with C-r bladder in the T1 stage is 12.5% †/ 56.2% / 31.25%, respectively, in healthy 13.3% / 50% / 36.7%. Of the 36 patients with Cr with bladder Cr in the T1 stage, 83.3% of patients showed G2 neoplasia, 11.1% found G3 neoplasia and 5.5% G1 in G1 patients. With T1G2 bladder cancer, the GG VEGF genotype was detected in 40 % of patients, GC in 26.7%, TNF-a genotype and GA were detected in 50% of patients, GG at 31.25%, and TNF-b gene genotype 43.7% and CC in 25% of patients.

Vascular Endothelial Growth Factor Gene Polymorphism Is Associated With Long-term Kidney Allograft Outcomes

IntroductionVascular endothelial growth factor (VEGF) regulates vasculogenesis in physiological and pathological states. We evaluated the role of VEGF single-nucleotide polymorphisms (SNPs) −1154 G/A, −2578 C/A, +936 C/T, and −2549 Ins/Del in chronic allograft nephropathy.MethodsBlood samples were collected before renal transplantation, and DNA was extracted. Genotyping of VEGF SNPs −1154 G/A (rs1570360), −2578 C/A (rs699947), +936 C/T (rs112005313), and −2549 Ins/Del (18bpindel) polymorphisms were carried out. Relative quantification of VEGF-A mRNA expression for 4 VEGF SNPs were quantified by the 2−ΔΔCt algorithm. Kidney allografts were categorized into graft loss (n = 98) and normally functioning (n = 174) groups. Genotype frequencies were calculated using additive, dominant, and recessive models. Hardy−Weinberg Equilibrium was assessed between outcome groups by standard procedure using χ2 analysis. The cumulative allograft survival was estimated by Kaplan−Meier analysis and compared among VEGF genotypes by the log-rank test. Study limitations were the lack of VEGF serum levels, donor-specific antigens, and protocol biopsies.ResultsThere was an association of AA (hazard ratio = 2.42, P = 0.0001) and CA (hazard ratio = 1.83, P = 0.009) genotypes of −2578 C/A SNP with graft loss. After adjustment for transplant-related covariates, associations of VEGF SNPs −2578 C/A and −2549 Ins/Del with graft failure were found to be significant. There was prolonged graft survival for cases with the CC genotype of VEGF −2578 C/A SNP. The carrier −2578*CC, −1154*GG, and +936*CC genotypes were shown to have a strongly protective association. There was no association with posttransplantation lymphomas.ConclusionRecipients of kidney allografts possessing low-producing VEGF genotypes are associated with less prolonged graft survival.

VEGF, VEGFR2 and GSTM1 polymorphisms in Outcome of Multiple Myeloma Patients in the Thalidomide Era

Introduction: Angiogenesis (AG) abnormalities are crucial in pathogenesis of multiple myeloma (MM), and give support to treat patients with antiangiogenic agents. However, patients with similar clinicopathological aspects may present distinct outcome under AG inhibitors treatment. Single nucleotide polymorphisms (SNPs) in genes involved in blood vessels formation may constitute a plausible explanation for this finding. The wild-type alleles of VEGF c.-2595C>A (rs699947), c.-1154G>A (rs1570360), c.-634G>C (rs2010963), c.*237C>T (rs3025039), VEGFR2 c.-906T>C (rs2071559) and c.889G>A SNPs (rs2305948) SNPs, and GSTM1 and GSTT1 genes determine higher production, transcriptional activity, binding efficiency or best-characterized regulator of VEGF. This study aimed to investigate the roles of VEGF c.-2595C>A, c.-1154G>A, c.-634G>C, c.*237C>T, VEGFR2 c.-906T>C, c.889G>A SNPs, and GSTM1 and GSTT1 genes in outcome of MM patients treated with thalidomide-based regimens. Patients and methods: The study comprised 102 MM patients diagnosed at the Haematology and Haemotherapy Centre of University of Campinas between June 2005 and June 2013. The tumor was diagnosed by standard criteriaand staged by International Staging System. Therapeutic regimens consisted in thalidomide combined with steroids and chemotherapy, followed or not by autologous steam cell transplantation (ASCT). Response was evaluated at the end of treatment using the International Myeloma Working Group guidelines. The follow-up of patients was performed with hematological, biochemical, and immunological exams. The end of the study was February 2016. Genotypes of VEGF, VEGFR2 SNPs, and GSTM1 and GSTT1 genes were analyzed in genomic DNA by polymerase chain reaction based methods. The pairwise linkage disequilibrium (LD) was performed to ensure that markers were appropriate for inclusion in the VEGF and VEGFR2 haplotype estimates. The chi-square test and logistic regression model were used to identify variables influencing response to treatment. The Kaplan-Meier method, log-rank test and Cox hazards models served to assess the associations between event-free survival (EFS) and overall survival (OS). Results: Near half of patients enrolled in this study were male, and most of them were caucasians and with tumor at stages II or III. ASCT was performed after chemotherapy in near 40% of patients. LDs between VEGF and VEGFR2 SNPs were seen in study, and common haplotypes (frequency >1%) of the genes were included in further analyses. Patients with the wild-type allele of VEGF c.-2595C>A alone or plus the wild-type allele of VEGFR2 c.-906T>C SNPs, and the CGGC haplotype of all respective VEGF SNPs had 3.55, 9.91, and 3.86 more chances of achieving better response to therapy than others. The median follow-up time of 102 MM patients enrolled in the study was 43 months (range: 1-88). The estimated probabilities of 60-months EFS and OS were 24.5% and 48.1%, respectively. At 60 months of follow-up, patients with VEGFR2 c.889GG, VEGF c.-634GG plus VEGFR2 c.889GG, and VEGFR2 c.889GGplus GSTM1 present genotypes had 2.62, 2.64, and 2.80 more chances of presenting disease relapse or progression, and 2.21, 4.88, and 4.23 more chances of evolving to death in multivariate analysis, respectively. Conclusion: Our data present, for the first time, a preliminary evidence that VEGF c.-2595C>A, c.-1154G>A, c.-634G>C, c.*237C>T, VEGFR2 c.-906T>C, c.889G>A SNPs, and GSTM1 gene alter outcome of MM patients treated with thalidomide-based regimens. If these findings could be confirmed in multi-center studies with larger sample size, this might constitute a promise in assisting optimal patient choice for treatment with angiogenic agents. Financial support: São Paulo Research Foundation (FAPESP). DisclosuresNo relevant conflicts of interest to declare.

VEGF, VEGFR2 and GSTM1 Polymorphisms in Outcome of Multiple Myeloma Patients in the Thalidomide Era

Introduction : Angiogenesis (AG) abnormalities are crucial in pathogenesis of multiple myeloma (MM), and give support to treat patients with antiangiogenic agents. However, patients with similar clinicopathological aspects may present distinct outcome under AG inhibitors treatment. Single nucleotide polymorphisms (SNPs) in genes involved in blood vessels formation may constitute a plausible explanation for this finding. The wild-type alleles of VEGF c.-2595C>A (rs699947), c.-1154G>A (rs1570360), c.-634G>C (rs2010963), c.*237C>T (rs3025039), VEGFR2 c.-906T>C (rs2071559) and c.889G>A SNPs (rs2305948) SNPs, and GSTM1 and GSTT1 genes determine higher production, transcriptional activity, binding efficiency or best-characterized regulator of VEGF. This study aimed to investigate the roles of VEGF c.-2595C>A, c.-1154G>A, c.-634G>C, c.*237C>T, VEGFR2 c.-906T>C, c.889G>A SNPs, and GSTM1 and GSTT1 genes in outcome of MM patients treated with thalidomide-based regimens. Patients and methods : The study comprised 102 MM patients diagnosed at the Haematology and Haemotherapy Centre of University of Campinas between June 2005 and June 2013. The tumor was diagnosed by standard criteriaand staged by International Staging System. Therapeutic regimens consisted in thalidomide combined with steroids and chemotherapy, followed or not by autologous steam cell transplantation (ASCT). Response was evaluated at the end of treatment using the International Myeloma Working Group guidelines. The follow-up of patients was performed with hematological, biochemical, and immunological exams. The end of the study was February 2016. Genotypes of VEGF , VEGFR2 SNPs, and GSTM1 and GSTT1 genes were analyzed in genomic DNA by polymerase chain reaction based methods. The pairwise linkage disequilibrium (LD) was performed to ensure that markers were appropriate for inclusion in the VEGF and VEGFR2 haplotype estimates. The chi-square test and logistic regression model were used to identify variables influencing response to treatment. The Kaplan-Meier method, log-rank test and Cox hazards models served to assess the associations between event-free survival (EFS) and overall survival (OS). Results : Near half of patients enrolled in this study were male, and most of them were caucasians and with tumor at stages II or III. ASCT was performed after chemotherapy in near 40% of patients. LDs between VEGF and VEGFR2 SNPs were seen in study, and common haplotypes (frequency >1%) of the genes were included in further analyses. Patients with the wild-type allele of VEGF c.-2595C>A alone or plus the wild-type allele of VEGFR2 c.-906T>C SNPs, and the CGGC haplotype of all respective VEGF SNPs had 3.55, 9.91, and 3.86 more chances of achieving better response to therapy than others. The median follow-up time of 102 MM patients enrolled in the study was 43 months (range: 1-88). The estimated probabilities of 60-months EFS and OS were 24.5% and 48.1%, respectively. At 60 months of follow-up, patients with VEGFR2 c.889GG, VEGF c.-634GG plus VEGFR2 c.889GG, and VEGFR2 c.889GGplus GSTM1 present genotypes had 2.62, 2.64, and 2.80 more chances of presenting disease relapse or progression, and 2.21, 4.88, and 4.23 more chances of evolving to death in multivariate analysis, respectively. Conclusion : Our data present, for the first time, a preliminary evidence that VEGF c.-2595C>A, c.-1154G>A, c.-634G>C, c.*237C>T, VEGFR2 c.-906T>C, c.889G>A SNPs, and GSTM1 gene alter outcome of MM patients treated with thalidomide-based regimens. If these findings could be confirmed in multi-center studies with larger sample size, this might constitute a promise in assisting optimal patient choice for treatment with angiogenic agents. Financial support : Sao Paulo Research Foundation (FAPESP). Disclosures No relevant conflicts of interest to declare.

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.

Allelic Polymorphism OF GENES OF FACTORS OF ANGIOGENESES in case of Genital Endometriosis

With the using modern molecular-genetic methods for the study it was shown that the allele C and genotypes GC and CC of the polymorphic variant G-405C of VEGF gene, allele A and genotypes GA and AA of the polymorphic region G-1154A of VEGF gene, allele C and genotypes ТС and СС of polymorphism T-604C of KDR gene as well as allele A and genotypes СА and GА of polymorphism G-735A of Ang2 gene predisposes to the development of genital endometriosis in women.

THE ANALYSIS OF CLINICAL, FUNCTIONAL, LABORATORY AND GENETIC PARAMETERS VALUES ON THE CONDITION OF PATIENTS AFTER MYOCARDIAL INFARCTION, AND PROGNOSIS OF INTRAMYOCARDIAL AUTOLOGIC CELL THERAPY EFFECTIVENESS FOR CHRONIC HEART FAILURE

АНАЛИЗ ИНФОРМАТИВНОСТИ КЛИНИЧЕСКИХ, ФУНКЦИОНАЛЬНЫХ, ЛАБОРАТОРНЫХ И ГЕНЕТИЧЕСКИХ ПОКАЗАТЕЛЕЙ ОЦЕНКИ СОСТОЯНИЯ ПАЦИЕНТОВ, ПЕРЕНЕСШИХ ИНФАРКТ МИОКАРДА, В ПРОГНОЗЕ ЭФФЕКТИВНОСТИ ИНТРАМИОКАРДИАЛЬНОЙ АУТОЛОГИЧНОЙ КЛЕТОЧНОЙ ТЕРАПИИ ХРОНИЧЕСКОЙ СЕРДЕЧНОЙ НЕДОСТАТОЧНОСТИ

Association of 18bp insertion/deletion polymorphism, at -2549 position of VEGF gene, with diabetic nephropathy in type 2 diabetes mellitus patients of North Indian population.

BackgroundVascular endothelial growth factor (VEGF) is a potent multifunctional cytokine which plays a key role in the pathogenesis of diabetic micro-vascular complications. Human VEGF gene is said to be highly polymorphic. Insertion/deletion (I/D) polymorphism of the 18 bp fragment at −2549 position of the promoter region in VEGF gene is said to be of particular interest. The study was aimed to evaluate association of Insertion/deletion (I/D) polymorphism of the 18 bp fragment at −2549 position of the promoter region in VEGF gene, with diabetic nephropathy in type 2 diabetes mellitus.MethodsThis cross sectional study enrolled 40 subjects each of diabetic nephropathy (DN), diabetes mellitus without nephropathy (DM) and normal control subjects. DNA was isolated from peripheral blood leukocytes. Genotyping of the VEGF gene insertion/ deletion (I/D) polymorphism was done by the polymerase chain reaction (PCR) methods. The frequency of VEGF alleles and genotype distribution were compared in diabetic nephropathy, uncomplicated diabetic and control groups.ResultsDD genotype and D allele were found to be significantly associated with DN group (p = 0.009 and 0.02 respectively) in comparison to DM group. Also DD genotype conferred significant risk of diabetic nephropathy in DM group (OR = 4.2) (against combined frequency of ID and II genotype) so does D allele 2.09 (against I allele).ConclusionDD genotype and D allele in I/D polymorphism at −2549 position of VEGF gene is associated with increased susceptibility to diabetic nephropathy in north Indian population.

Association between SNPs in vascular endothelial growth factor polymorphisms and risk of renal cell carcinoma: a case-control study.

We conducted this case-control study to assess the role of the VEGF -2578C/A, +1612G/A, +936C/T and -634G/C gene polymorphisms in the development of renal cell carcinoma (RCC). A hospital-based case-control study was conducted in a 360 consecutive primary RCC patients and 360 age and gender-matched controls during January 2010 and January 2014. The polymerase chain reaction-restriction fragment length polymorphism was used for VEGF -2578C/A, +1612G/A, +936C/T and -634G/C genotyping. Multivariate conditional logistic regression analyses showed that subjects carrying the AA and the CA+AA genotypes of VEGF -2578C/A had significant association with increased risk of RCC compared to those having the CC genotype, and the ORs (95%CI) were 1.77 (1.10-2.85) and 1.37 (1.01-1.86), respectively. Using the conditional logistic regression model, CA+AA genotype of VEGF -2578C/A had a significantly increased risk of RCC in ever cigarette smokers, and individuals with hypertension, and the ORs (95%CI) were 1.93 (1.08-3.45) and 2.57 (1.06-6.57), respectively. In conclusion, our results showed that AA genotype of VEGF -2578C/A genetic variants is associated with increased risk of RCC.