Vascular Endothelial Growth Factor Rs2010963 Research Articles

The evaluation of VEGF and HIF-1α gene polymorphisms and multiple sclerosis susceptibility.

Multiple sclerosis (MS) is an autoimmune disease that leads to myelin sheath destruction. Hypoxia-inducible factor 1 (HIF-1) has several roles in cells, such as inducing inflammation and angiogenesis. Recently, several lines of evidence have indicated the role of the hypoxia response and the HIF-1 signaling pathway in an autoimmune disease such as MS. The present study aimed to evaluate the effects of HIF-1α gene polymorphisms and vascular endothelial growth factor (VEGF) (as a major target gene of HIF-1α) gene polymorphism on MS susceptibility. In total, 150 MS patients and 150 healthy age- and gender-matched people as a control group participated in the present study. The polymerase chain reaction-restriction fragment length polymorphism method was used for genotyping. The results obtained showed that the CC genotype of the VEGF rs699947 polymorphism was significantly higher in the case group than in the control group (p = 0.004). Also, we showed a significant relationship between the VEGF rs699947 polymorphism and MS in a dominant inheritance model (p = 0.005). Regarding the VEGF rs699947 polymorphism allelic distribution, the C allele frequency was significantly higher in the control group than in the case group (71.3% versus 61%, respectively, p = 0.009) and decreased the MS susceptibility by 1.6-fold (odds ratio = 1.6, 95% confidence interval = 1.2-2.2). There was no significant difference between the two groups with respect to HIF-1α rs11549465 genotypic distribution. The HIF-1α C111A polymorphism was non-polymorphic in our study population, except in the case group where nine subjects carried the CA genotype. We show a significant association between VEGF rs60047 polymorphism and MS susceptibility. However, our results do not show a significant association between MS and HIF-1α polymorphisms.

Vascular endothelial growth factor polymorphism rs2010963 status does not affect patent ductus arteriosus incidence or cyclooxygenase inhibitor treatment success in preterm infants.

Vascular endothelial growth factor is critically involved in ductus arteriosus closure. Polymorphisms in the vascular endothelial growth factor gene have been associated with several diseases in neonates and adults. Herein, we investigated if vascular endothelial growth factor polymorphism rs2010963 status is associated with patent ductus arteriosus incidence and/or pharmacological treatment success. We assessed rs2010963 status in 814 preterm infants (<1500 g birth weight) by means of restriction fragment length polymorphism analysis. DNA samples were obtained from dry-spot cards used for the German national newborn screening program. Clinical data were obtained by retrospective chart review. We could not find any statistically significant difference in the incidence of patent ductus arteriosus depending on vascular endothelial growth factor rs2010963 polymorphism status. Furthermore, no statistically significant associations between vascular endothelial growth factor polymorphism rs2010963 status and cyclooxygenase inhibitor treatment success were observed. Our results indicate that there is no association between vascular endothelial growth factor polymorphism rs2010963 status and the occurrence of patent ductus arteriosus or the response to cyclooxygenase inhibitor treatment in a large cohort of preterm infants. Additional studies are needed to determine the role of genetic factors on patent ductus arteriosus incidence and treatment response.

Epistatic Interaction Between 5-HT1A and Vascular Endothelial Growth Factor Gene Polymorphisms in the Northern Chinese Han Population With Major Depressive Disorder.

Aims: Serotonin 1A receptor (5-HT1A) and vascular endothelial growth factor (VEGF) are widely expressed in the neurons of the hippocampus and have significant roles in the pathophysiological processes of major depressive disorders (MDDs). The present study was designed to examine 5-HT1A and VEGF gene polymorphisms and whether the gene–gene interaction of 5-HT1A and VEGF gene variants was associated with MDD. Methods: A total of 264 MDD patients and 264 healthy controls were included in the present genetic study. The rs6295, rs1364043, and rs878567 single-nucleotide polymorphisms (SNPs) in the 5-HT1A gene and the rs699947, rs833061, and rs2010963 SNPs in the VEGF gene were selected for genotypic analyses. The generalized multifactor dimensionality reduction method was employed to assess their interactions. Results: The genotype distributions of the two genes’ respective SNPs were significantly different between patients and controls for 5-HT1A rs6295 (p = 0.041) and VEGF rs2010963 (p = 0.035); however, no significant allelic variation in 5-HT1A (rs6295, rs1364043, and rs878567) and VEGF (rs699947, rs833061, and rs2010963) was found. The interactions between 5-HT1A (rs6295, rs1364043, and rs878567) and VEGF (rs699947, rs833061, and rs2010963) had a cross-validation (CV) consistency of 10/10 and a p value of 0.0107, which was considered as the best generalized multifactor dimensionality reduction (GMDR) model. Conclusions: The interactions between 5-HT1A and VEGF gene polymorphisms may play a key role in the development of MDD in the Northern Chinese Han population.

Investigation of Immunovascular Polymorphisms and Intersections in Psoriasis.

Background:Psoriasis is a chronic, inflammatory skin disease. The etiology of the disease is unknown. It is a polygenic and multifactorial disease, which interacts with genetic and environmental factors. Genetic factors (polymorphism/mutation) can alter the immune system and normal physiologically functioning keratinocytes to pathological or predisposition levels.Aims:We aimed to investigate psoriasis at a different and novel window by searching for vascular and immunological variations and intersections in psoriasis. We investigated the main vascular and hypoxic controlling factors, which are vascular endothelial growth factor (VEGF) and hypoxia inducible factor 1 alpha (HIF-1α), as well as immunological and serotonergic factors, such as TNF-α, IL-10, and 5HT2A, which could connect each other to the pathogenesis of psoriasis.Subjects and Methods:Nine single nucleotide polymorphisms (SNPs) in five genes were genotyped by mini-array format in 300 subjects: VEGF (rs2010963, rs833061, and rs1570360), HIF-1α (rs11549465), TNF-α (rs361525, rs1799964, and rs1800629), IL-10 (rs1800896), and 5HT2A (rs6311).Results:An association was found between rs1800629 (TNF-α) and Type I psoriasis, and rs833061 (VEGF) and Type II psoriasis. Haplotype analysis suggests that the coexistence of the polymorphisms rs1799964 (TNF-α), rs2010963 (VEGF), rs833061 (VEGF), and rs6311 (5HT2A) may be a protective factor for psoriasis.Conclusion:Our results suggest that the vascular component of the studied vasculo-immunologic variation is more relevant in the pathogenesis of psoriasis.

Association of vascular endothelial growth factor gene polymorphisms with Crohn's disease among Chinese patients

To assess the association of vascular endothelial growth factor (VEGF) gene polymorphisms with susceptibility to Crohn's disease (CD) in a Chinese population. For 275 CD patients and 495 controls, the genotypes of VEGF gene rs699947 and rs3025039 loci were determined with a SNaPshot method. The allelic and genotypic frequencies of the rs699947 and rs3025039 loci did not differ between the two groups (all P>0.05). By stratification analysis, allele A and genotype CA+AA of rs699947 were more frequent in patients with colonic CD compared with the controls (P=0.006, 95%CI:1.143-2.234; P=0.005, 95%CI:1.203-2.900, respectively). Compared with the controls, the allele A and genotype CA+AA of rs699947 were less frequent in patients with ileal lesions including ileal CD and ileocolonic CD (P=0.033, 95%CI:0.524-0.974;P=0.043, 95%CI:0.481-0.989, respectively). The frequency of TT homozygote of rs3025039 was lower in patients with non-stricturing and non-penetrating CD compared with the controls (P=0.036, 95%CI:0.016-0.870). Polymorphisms of the VEGF gene rs699947 locus may contribute to an increased risk for colonic CD, but may play a protective role in patients with ileal lesion. Individuals carrying the TT genotype for VEGF rs3025039 locus may be less susceptible to non-stricturing and non-penetrating CD.

Vascular endothelial growth factor gene polymorphisms and coronary heart disease: a systematic review and meta-analysis

We performed this study to better elucidate the relationship between vascular endothelial growth factor (VEGF) polymorphisms and coronary heart disease (CHD). Eligible articles were searched in PubMed, Medline, Embase, Scopus and CNKI. A total of 24 studies containing 6489 CHD patients and 5664 control subjects were analyzed. Our overall and subgroup analyses suggested that rs699947 polymorphism was significantly associated with CHD susceptibility in both Caucasians and Asians, rs1570360 polymorphism was significantly associated with CHD susceptibility in Caucasians, and rs3025039 polymorphism was significantly associated with CHD susceptibility in Asians. Besides, rs3025039 polymorphism was significantly correlated with the number of affected coronary arteries, while rs699947 and rs2010963 polymorphisms were significantly correlated with poor collateral circulation in CHD patients. Overall, our findings indicate that VEGF rs699947, rs1570360, and rs3025039 polymorphisms may affect CHD susceptibility. Moreover, VEGF rs699947 and rs2010963 polymorphisms may serve as genetic biomarkers of poor collateral circulation after myocardial ischemia.

Association of genetic polymorphisms in vascular endothelial growth factor with susceptibility to coronary artery disease: a meta\u2013analysis

BackgroundSingle nucleotide polymorphisms (SNPs) located in the vascular endothelial growth factor (VEGF) gene may be correlated with the susceptibility to coronary artery disease (CAD) – although results have been controversial. The aim of this meta–analysis is to clarify the effects of VEGF –2578A/C (rs699947), −1154G/A (rs1570360), +405C/G (rs2010963), and + 936C/T (rs3025039) polymorphisms on CAD risk.MethodsPooled odds ratio (OR) and corresponding 95% confidence intervals (CIs) were calculated to estimate the strength of the association between VEGF gene polymorphisms and CAD risk. Fixed- or random-effects model was used depending on the heterogeneity between studies.ResultsIn total, 13 eligible articles containing 29 studies were analysed. The pooled analysis indicated that the VEGF gene polymorphisms of rs699947, rs2010963, and rs3025039 were associated with an increased risk of CAD, whereas no significant associations were observed with the rs1570360 polymorphism. A subgroup analysis stratified by ethnicity revealed that the rs699947 and rs3025039 polymorphisms were associated with CAD risk in Asian populations. In addition, stratification by control source indicated an increased risk of CAD susceptibility with the rs699947 polymorphism for population–based studies of reduced heterogeneity.ConclusionsIn summary, we concluded that the VEGF gene polymorphisms rs699947, rs2010963, and rs3025039 are correlated with an elevated CAD risk.

Association between VEGF genetic variants and diabetic foot ulcer in Chinese Han population: A case-control study.

The aim of this study was to investigate the association of vascular endothelial growth factor (VEGF) gene polymorphisms with diabetic foot ulcer (DFU) susceptibility in a Chinese Han population.Around 88 type 2 diabetes mellitus (T2DM) patients without DFU and 97 T2DM patients with DFU were enrolled in this study. A total of 103 age and gender matched healthy individuals were recruited as healthy control. VEGF gene polymorphisms rs699947 and rs13207351 were analyzed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. Odds ratio (OR) with 95% confidence interval (CI) was calculated to assess the association between VEGF gene polymorphisms and DFU risk.The frequency of AA and AC genotypes of rs699947 were lower in DFU patients than that in healthy controls (P = .020, P = .031), suggesting that AC and AA genotypes were negatively associated with DFU risk originating from healthy individuals (OR = 0.496, 95%CI = 0.274–0.899; OR = 0.130, 95%CI = 0.015–1.112). Significantly decreased trend of rs699947 A allele was observed in DFU patients when compared to the controls (P = .004), suggesting A allele was distinctly correlated with decreased DFU risk (OR = 0.490, 95%CI = 0.298–0.804). But no significant differences were detected in rs13207351 genotype and allele distributions between patients and control groups (P > .05).Individuals carrying VEGF rs699947 A allele show low susceptibility to DFU in the Chinese Han population.

Vascular endothelial growth factor (VEGF) gene polymorphisms (rs699947, rs833061, and rs2010963) and psoriatic risk in South Indian Tamils

BackgroundPsoriasis is a chronic inflammatory disease of the skin. Vascular endothelial growth factor (VEGF), a pro-angiogenic factor, is involved in the pathogenesis of psoriasis. Being highly polymorphic, several SNPs of VEGF have been reported to be associated with increased risk of psoriasis. ObjectivesWe determined the association of VEGF gene polymorphisms with risk of psoriasis in South Indian Tamils. Methods300 cases of psoriasis and 300 controls were recruited in this case-control study. Genotyping of SNPs of VEGF gene was done using Taqman 5′ allele discrimination assay. Estimation of VEGF levels in plasma was done by ELISA. ResultsVEGF (rs2010963) polymorphism and the CTC haplotype were found to confer an increased risk of psoriasis. However, two other VEGF SNPs, rs833061, and rs699947, showed no association with psoriasis susceptibility. VEGF levels were higher in patients with psoriasis, as compared with controls and significantly correlated with disease severity. ConclusionsOur results indicate that VEGF (rs2010963) polymorphism and CTC haplotype of the VEGF SNPs (rs699947, rs833061, and rs2010963) confer an increased risk of psoriasis in the South Indian Tamil population. Plasma VEGF levels are higher in patients with psoriasis, as compared with controls and are significantly correlated with disease severity.

Association between three VEGF polymorphisms and renal cell carcinoma susceptibility: a meta-analysis.

Several studies have reported an association between vascular endothelial growth factor (VEGF) gene polymorphisms rs2010963, rs3025039 and rs699947 and renal cell carcinoma (RCC). However, the results remain inconclusive and controversial. We therefore conducted a meta-analysis to evaluate this association. Electronic databases were searched for relevant case-control studies up to November 2016. RevMan 5.2 software and STATA version 12.0 were used for statistical analysis in our meta-analysis. Heterogeneity was assessed using the I2 value. Nine eligible studies were retrieved for detailed evaluation. The pooled estimates indicated that the GG genotype of VEGF rs2010963 polymorphism significantly decreased RCC risk [GG vs. GC+CC; GG vs. GC]. There was also a significant association between VEGF rs3025039 polymorphism and RCC susceptibility [CC+CT vs. TT; CC vs. TT]. Furthermore, a significant association between VEGF rs699947 polymorphism and RCC susceptibility was detected [A vs. C; AA+AC vs. CC; AA vs. AC+CC; AA vs. CC; AA vs. AC; AC vs. CC]. Subgroup analysis revealed that these associations held true especially for Asians. Our meta-analysis suggested that there may be a relationship between the VEGF rs2010963, rs3025039 and rs699947 polymorphisms and RCC susceptibility.

Interactions between the vascular endothelial growth factor gene polymorphism and life events in susceptibility to major depressive disorder in a Chinese population

BackgroundRecent studies suggest that vascular endothelial growth factor (VEGF) is involved in the development of major depressive disorder. The aim of this study is to investigate the interaction between vascular endothelial growth factor (VEGF) polymorphism (+405G/C, rs2010963) and negative life events in the pathogenesis of major depressive disorder (MDD). MethodsDNA genotyping was performed on peripheral blood leukocytes in 274 patients with MDD and 273 age-and sex-matched controls. The frequency and severity of negative life events were assessed by the Life Events Scale (LES). A logistics method was employed to assess the gene-environment interaction (G×E). ResultsDifferences in rs2010963 genotype distributions were observed between MDD patients and controls. Significant G×E interactions between allelic variation of rs2010963 and negative life events were observed. Individuals carrying the C alleles were susceptible to MDD only when exposed to high-negative life events. ConclusionsThese results indicate that interactions between the VEGF rs2010963 polymorphism and environment increases the risk of developing MDD.

Vascular endothelial growth factor A polymorphisms are associated with increased risk of coronary heart disease: a meta-analysis.

Coronary heart disease (CHD) is a common complex disease resulting from the interaction of multiple environmental and genetic factors. To assess the potential relationship of vascular endothelial growth factor (VEGFA) rs699947 C>A, rs3025039 C>T and rs2010963 G>C polymorphisms with CHD risk, a comprehensive meta-analysis was conducted. A systematic search of EMBASE and PubMed online database for publications on VEGFA polymorphisms and risk of CHD was carried out. Crude Odds ratios (ORs) with their 95% confidence intervals (CIs) were calculated to determine the association. A total of ten publications including 22 trails involving 2097 cases and 2867 controls were included in our pooled analysis. Overall, results of the present meta-analysis demonstrated a significant association between VEGFA rs699947 C>A polymorphism and an increased risk of CHD. After stratifying by ethnicity and CHD type, the association was also obtained. A significant association between VEGFA rs3025039 C>T polymorphism and risk of CHD was also found. For VEGFA rs2010963 G>C polymorphism, the polymorphism was associated with MI risk. In conclusion, our findings suggest that VEGFA rs699947 C>A, rs3025039 C>T and rs2010963 G>C polymorphisms are risk factors for CHD. In the future, large sample size and well-designed epidemiologic studies are needed to confirm these conclusions.

The impact of vascular endothelial growth factor +405 C/G polymorphism on long-term outcome and severity of coronary artery disease.

The association between genetic variations of vascular endothelial growth factor (VEGF) gene and the risk for atherosclerosis has been hypothesized. We aimed to assess the relationship between rs2010963 (+405 C/G) polymorphism and presence, severity, and outcome of coronary artery disease (CAD) in an Iranian cohort. Genotyping of VEGF rs2010963 polymorphism was performed on 520 individuals, comprising 347 patients with documented coronary artery disease based on angiography report and 173 individuals with normal coronary arteries, using the TaqMan real-time PCR method. In final, 484 subjects were followed up over a 5-year period for cardiovascular-related outcomes. C allele of VEGF rs2010963 polymorphism was related to increase risk for CAD and also slightly to 5-year cardiovascular mortality. The 5-year survival in C and G allele subgroups were 92.3% and 94.3% in CAD group and 95.7% and 98.0% in non-CAD group, respectively. Vascular endothelial growth factor rs2010963 polymorphism may be associated with the presence of CAD and its long-term survival, but not with its severity. To the best of our knowledge, this is the first report of genetic association between rs2010963 SNP and CAD-related death. It can be thus suggested that rs2010963 VEGF gene can be considered as a genetic risk predictor for CAD and its outcomes.

Associations of the VEGF level, VEGF rs2010963 G/C gene polymorphism and ankylosing spondylitis risk in a Chinese Han population

To investigate the roles of the plasma vascular endothelial growth factor (VEGF) level and VEGF gene polymorphisms in ankylosing spondylitis (AS) susceptibility. The plasma VEGF level was measured using an enzyme-linked immunosorbent assay. The VEGF rs2010963 G/C gene polymorphism was analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Our data indicated that the average plasma VEGF concentration in the AS patients was markedly higher than in the controls. Stratification analysis indicated a significant correlation between an elevated plasma VEGF level in AS patients and sex, but not age, HLA-B27, C-reactive protein (CRP), or grade of the sacroiliac joint. We also found that VEGF rs2010963 G/C was associated with a decreased risk of AS. Significant differences were found between the VEGF rs2010963 G/C genotypes and elevated plasma level in AS patients when compared with the controls. However, we did not find a significant association between the plasma VEGF level and different rs2010963 G/C genotypes in the AS patients or controls. To sum up, serum VEGF levels are significantly associated with the inflammatory process of AS. This study suggests that VEGF is involved in the immunological or inflammatory process of AS.

Association of Genetic Polymorphisms on Vascular Endothelial Growth Factor and its Receptor Genes with Susceptibility to Coronary Heart Disease.

BackgroundCoronary heart disease (CHD) is a cardiovascular disease characterized by high morbidity and mortality. Vascular endothelial growth factor (VEGF) and its receptor, named kinase insert domain-containing receptor (KDR, or VEGFR2), which are involved with angiogenesis and vascular repair, could partly contribute to the development of CHD. The aim of this study, therefore, was to investigate the potential correlations between genetic polymorphisms on VEGF and KDR and susceptibility to CHD, and the integrative role of SNPs combined on susceptibility to CHD were also studied.Material/MethodsVenous blood samples gathered from 533 DCM patients and 533 healthy controls were used to genotype tag-SNPs of VEGF (rs699947, rs2010963, and rs3025010) and KDR (rs2071559, rs2305948, and rs1870377) by polymerase chain reaction (PCR) and SNaPshot assay. Investigations of potential haplotypes were conducted on the basis of SHEsis software. The odds ratio (ORs) and relevant 95% confidence intervals (95% CI) were used to estimate associations of SNPs/haplotypes with risk of CHD. Multivariate logistic regression was also performed, taking certain clinical characteristics (e.g., BMI, smoking, alcohol consumption, diabetes, and hypertension) into consideration. All statistical analyses were done with STATA Version 12.0 software.ResultsOur results suggest that rs699947 (T>C) on KDR are associated with susceptibility to CHD under the dominant model before (OR=1.35, 95% CI: 1.05–1.73, P=0.019) and after (OR=1.33, 95% CI: 1.01–1.76, P=0.044), allowing for clinical characteristics (e.g., BMI, smoking, alcohol consumption, diabetes, and hypertension). rs2305948 (G>A) and rs1870377 (A>T) on VEGF were also found to be associated with risk of CHD under the recessive model after adjustment with multivariate regression analyses (OR=1.21, 95% CI: 1.02–1.43, P=0.029; OR=2.54, 95% CI: 1.13–5.75, P=0.025); OR=2.83, 95% CI: 1.47–5.46, P=0.002, respectively). Additionally, haplotype analyses revealed that integration of 5 SNPs would either raise (e.g. C-C-T-G-T and T-G-T-G-T) or reduce (e.g. C-C-C-G-T, T-C-T-G-A, T-C-T-G-T, and T-G-T-G-A) risk of CHD.ConclusionsGenetic polymorphisms on VEGF (rs699947) and KDR (rs2305948and rs1870377), as well as relevant haplotypes, may serve as genetic markers that might be useful in future investigations on the pathogenesis of CHD.

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 Gene Polymorphism (rs2010963) and Its Receptor, Kinase Insert Domain-Containing Receptor Gene Polymorphism (rs2071559), and Markers of Carotid Atherosclerosis in Patients with Type 2 Diabetes Mellitus.

Background. The current study was designed to reveal possible associations between the polymorphisms of the vascular endothelial growth factor (VEGF) gene (rs2010963) and its receptor, kinase insert domain-containing receptor (KDR) gene polymorphism (rs2071559), and markers of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Patients and Methods. 595 T2DM subjects and 200 control subjects were enrolled. The carotid intima-media thickness (CIMT) and plaque characteristics (presence and structure) were assessed ultrasonographically. Biochemical analyses were performed using standard biochemical methods. Genotyping of VEGF/KDR polymorphisms (rs2010963, rs2071559) was performed using KASPar assays. Results. Genotype distributions and allele frequencies of the VEGF/KDR polymorphisms (rs2010963, rs2071559) were not statistically significantly different between diabetic patients and controls. In our study, we demonstrated an association between the rs2071559 of KDR and either CIMT or the sum of plaque thickness in subjects with T2DM. We did not, however, demonstrate any association between the tested polymorphism of VEGF (rs2010963) and either CIMT, the sum of plaque thickness, the number of involved segments, hsCRP, the presence of carotid plaques, or the presence of unstable carotid plaques. Conclusions. In the present study, we demonstrated minor effect of the rs2071559 of KDR on markers of carotid atherosclerosis in subjects with T2DM.

Genetic association between VEGF polymorphisms and BRONJ in the Korean population.

The purpose of this study was to evaluate the association between vascular endothelial growth factor (VEGF) polymorphisms and bisphosphonate-related osteonecrosis of the jaw (BRONJ) in the Korean population. Forty-five individuals (2 men, 43 women; mean age: 68.7 ± 12.3 years) were recruited for this study. All visited the Yonsei University Dental Hospital for surgical intervention from January 2012 to January 2013 and had a history of bisphosphonate (BP) administration (oral and/or intravenous). Patients were allocated to case (n = 26) or control (n = 19) groups according to the patients' selection criteria. Association between three VEGF single nucleotide polymorphisms (rs699947 (-2578 C>A), rs2010963 (-634 G>C) and rs3025039 (+936 C>T)) and BRONJ were investigated using multiple logistic regression analysis and Fisher's exact test where appropriate (α = 0.05). The CC homozygotes of rs2010963 and rs3025039 of VEGF gene were associated with an increased risk of BRONJ (P = 0.04, 0.03, respectively). In haplotype analysis, no differences in haplotype C-C (-2578/-634) and haplotype C-C-C (-2578/-634/+936) were observed. The CC homozygotes of rs2010963 and rs3025039 polymorphisms in the VEGF gene were associated with an increased risk of BRONJ in the Korean population. Further epidemiological cohort studies with a larger sample size would be required to confirm the suggestive correlations.

Combination of Angiotensin Converting Enzyme Insertion/Deletion (I/D) (rs4646994) and VEGF Polymorphism (+405G/C; rs2010963) Synergistically Associated With the Development, of Albuminuria in Iranian Patients With Type 2 Diabetes.

Background:Angiotensin-converting enzyme (ACE) insertion/deletion (I/D) and vascular endothelial growth factor (VEGF) polymorphisms have been shown to associate with diabetic nephropathy (DN).Objectives:We examined the hypothesis that ACE-D and VEGF-G alleles act synergistically in association with DN, in patients with type 2 diabetes mellitus (T2DM).Patients and Methods:The VEGF (rs2010963) and ACE (rs4646994) genotypes were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 490 T2DM patients. Diabetic patients were classified as T2DM patients with and without albuminuria (control). The PCR and RFLP were used to detect the VEGF and ACE alleles.Results:A total of 255 consecutive patients with T2DM and microalbuminuria (Group A) and 235 patients with T2DM and normoalbuminuria (Group B) were included in the study. In univariate analysis, the groups were statistically similar for all variables, except for glycated hemoglobin (HbA1c) (P = 0.034), and the frequency of ACE (P = 0.015) and VEGF (P = 0.006) genotypes. Our study showed that the VEGF-G and ACE-D alleles are independently associated with the development of nephropathy. According to our data, the combination of these two risk factors had a significant synergistic effect on the risk of microalbuminuria development.Conclusions:Our study indicated that ACE-D and VEGF-G alleles can be an independent risk factor for microalbominuria in T2DM patients.

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

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