Endothelial Growth Factor Gene Polymorphisms Research Articles

Adverse Prognostic Impact of Vascular Endothelial Growth Factor Gene Polymorphism in Patients with Non-Hodgkin Lymphoma.

AbstractAbstract 2674Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis and progression of many types of cancer, and VEGF expression has been known to be associated with polymorphism of gene. However, the impact of polymorphisms of the VEGF gene on non-Hodgkin lymphoma (NHL) prognosis has not been fully elucidated. Here we investigated the association between VEGF polymorphisms and prognosis of NHL. The study involved 96 NHL patients treated at National Cancer Center, Korea. The median patient age was 57 years, and 60 patients (62.5%) were men. A total of 5 polymorphisms with heterozygous allele were analyzed. Clinical characteristics (e.g., cell lineage) and international prognostic index (IPI), including age, performance, LDH, stage and extra-nodal involvement, were evaluated and related to VEGF polymorphism. Hazard ratios (HRs) were determined in terms of risk for overall survival using Cox proportional hazard regression analysis. Diffuse large B cell lymphoma (n=73) was most common histologic type, and others were as follows: T-cell lymphoma (n=14), mantle cell lymphoma (n=6), and Burkitt lymphoma (n=3). IPI and stage were predictors for prognosis (p <0.01), and both index did not have correlation with VEGF polymorphisms. The genotype frequency of rs1570360 was GG (70%), GA (26%), and AA (4%), and it has significantly association with poor prognosis with HRs of 2.52 [95% confidence interval (CI), 1.36 to 4.67] in NHL patients and 2.41 [95% confidence interval (CI), 1.15 to 5.05] in DLBCL treated by rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), respectively. In IPI subgroup analysis, rs1570360 had association in higher IPI group (IPI ≥ 3) (p=0.02). These findings suggest that VEGF polymorphisms may be significant prognostic indicators for patients with NHL and DLBCL. Disclosures:No relevant conflicts of interest to declare.

Prognostic significance of vascular endothelial growth factor gene polymorphisms in patients with colorectal cancer

Angiogenesis plays an important role in tumor development, progression, and metastasis. Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis. However, the contribution of common VEGF polymorphisms to colorectal cancer (CRC) prognosis remains unclear. We have genotyped four polymorphisms of VEGF (-2578C>A, -1154G>A, -634G>C, and 936C>T) in 350 CRC cases from the Korean population. The genotyping of VEGF polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism assay. Although not every VEGF polymorphism was significantly correlated with patient prognosis in overall 350 CRC patients, we found that the VEGF -2578CA genotype was associated with a significantly poor prognosis for rectal cancers compared to the CC genotype (HR=2.156; 95% CI 1.090-4.267; P=0.028). In addition, we found that the -2578A/-1154G/-634G/+936C haplotype was significantly associated with a decreased overall survival (OS) rate in all 350 CRC patients (HR=2.530; 95% CI 1.340-4.780; P=0.004). In combination analysis, we found that the combined VEGF -2578CA+AA/-1154GG genotype was associated with a poor OS rate in all 350 CRC patients (HR=2.068; 95% CI 1.159-3.693; P=0.015). The VEGF gene polymorphisms investigated in this study were not found to be independent prognostic markers in Korean CRC populations. However, our results suggest that the VEGF -2578C>A variant may be a potential genetic marker for rectal cancer prognosis. Further large population studies are warranted to define whether the -2578C>A polymorphism is a prognostic marker of rectal cancer.

Association of the Vascular Endothelial Growth Factor Gene Polymorphisms (–460C/T, +405G/C and +936T/C) with Endometriosis: A Meta‐Analysis

Published data on the association between the vascular endothelial growth factor (VEGF) gene -460C/T (rs833061), +405G/C (rs2010963), +936T/C (rs3025039) polymorphisms and endometriosis risk are inconclusive. Eleven eligible case-control studies including 2690 cases and 2803 controls were included in this meta-analysis through searching the databases of PubMed and CBMdisc (up to August 1, 2011). In the overall analysis, no significant association between the -460C/T and +405G/C polymorphisms and risk of endometriosis was observed. However, significant associations were observed between endometriosis risk and VEGF+936T polymorphism with summarized odds ratio of 1.19 (95%CI, 1.02-1.37), 1.18 (95%CI, 1.03-1.37), 1.15 (95%CI, 1.01-1.30) for CT versus CC genotype, dominant mode (CT/TT vs. CC) and allele comparison (T vs. C), respectively. Furthermore, stratified analysis showed that significantly strong association between +936T/C polymorphism and endometriosis was present only in stage III-IV (OR = 1.32 for dominant mode; OR = 1.30 for T vs. C), but not in stage I-II. However, no significantly increased risk of endometriosis was found in any of the genetic models in Asians or in Caucasians. This meta-analysis supports that VEGF+936T/C polymorphism is capable of causing endometriosis susceptibility.

Association of VEGF gene polymorphisms with advanced retinopathy of prematurity: a meta-analysis

Published data on the association of vascular endothelial growth factor (VEGF) gene polymorphisms with retinopathy of prematurity (ROP) are inconclusive. The aim of the study was to assess the association by using meta-analysis. Data were collected from the following electronic databases: PubMed, Elsevier Science Direct, Excerpta Medica Database, Cochrane Library and China National Knowledge Infrastructure, with the last report up to 30 April, 2012. The odds ratio (OR) and its 95 % confidence interval (95 %CI) were used to assess the strength of the association. Meta-analysis was performed in a fixed/random effect model by using the software Review Manager 4.2. A total of 7 studies based on the search criteria were involved in this meta-analysis. Meta-analysis was performed for four VEGF gene polymorphisms (-634G/C, -460T/C, -2578C/A and 936C/T). Significant association was found for -460T/C polymorphism (C vs T: OR = 0.74, 95 %CI = 0.57-0.95, P = 0.02; TC+CC vs TT: OR = 0.75, 95 %CI = 0.47-1.21, P = 0.24; CC vs TT+TC: OR = 0.45, 95 %CI = 0.26-0.76, P = 0.003; CC vs TT: OR = 0.45, 95 %CI = 0.24-0.84, P = 0.01; TC vs TT: OR = 0.96, 95 %CI = 0.59-1.57, P = 0.87) in the VEGF gene, but not for other polymorphisms (-634G/C, -2578C/A and 936C/T). This meta-analysis demonstrates that advanced ROP is associated with VEGF gene -460T/C polymorphism, but not -634G/C, -2578C/A and 936C/T.

Associations of vascular endothelial growth factor (VEGF) gene and cytokine (IL-1B, IL-4, IL-6, IL-10, TNFA) genes combinations with type 2 diabetes mellitus in women

Aim. To study the association between vascular endothelial growth factor (VEGF) and cytokine (IL1B, IL4, IL6, IL10 and TNFA)gene polymorphism combinations with type 2 diabetes mellitus (T2DM) in women. Materials and methods. 374 Caucasian women without carbohydrate metabolism disorders from 23 to 68 years of age and 212 womenwith T2DM from 28 to 69 years of age were included in the study. The combinations of polymorphism А-2578С, С+936Т in VEGFgene with polymorphism in IL1B С-31Т, IL4 С-590Т, IL6 G-174C, IL10 A-592C and А-1082G, TNFA А-238G, A-308G and A-863Cwere studied. Results. Analysis revealed 52 combined genetic variations with different rate of occurrence between diabetic and control groups(р

1080P - Adverse Prognostic Impact of Vascular Endothelial Growth Factor Gene Polymorphism in Patients with Non-Hodgkin Lymphoma

ABSTRACT Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis and progression of many types of cancer and VEGF expression has been known to be associated with polymorphism of gene. However, the impact of polymorphisms of the VEGF gene on non-Hodgkin lymphoma (NHL) prognosis has not been fully elucidated. Here we investigated the association between VEGF polymorphisms and prognosis of NHL. The study involved 96 NHL patients treated at the National Cancer Center, Korea. The median patient age was 57 years, and 60 patients (62.5%) were men. A total of 5 polymorphisms with heterozygous allele were analyzed. Clinical characteristics (e.g., cell lineage) and international prognostic index (IPI), including age, performance, LDH, stage and extra-nodal involvement, were evaluated and related to VEGF polymorphism. Hazard ratios (HRs) were determined in terms of risk for overall survival using Cox proportional hazard regression analysis. Diffuse large B cell lymphoma (n = 73) was most common histologic type, and others were as follows: T-cell lymphoma (n = 14), mantle cell lymphoma (n = 6), and Burkitt lymphoma (n = 3). IPI and stage were predictors for prognosis (p Disclosure All authors have declared no conflicts of interest.

The relation of vascular endothelial growth factor (VEGF) gene polymorphisms on VEGF levels and the risk of vasoocclusive crisis in sickle cell disease

The association of vascular endothelial growth factor (VEGFA) variants and VEGF secretion with sickle cell disease (SCD) vasoocclusive crisis (VOC) was investigated in 210 VOC patients and 114 pain-free control patients. VEGFA -2578C/A (rs699947), -460T/C (rs833061), -1154G/A (rs15703060), -634G/C (rs2010963), 398G/A (rs833068), 497G/A (rs833070), -583T/C (rs3025020), and 936C/T (rs3025039) were carried out by real-time PCR. Higher frequency of rs2010963 C-allele, rs833068 A-allele, and rs3025020 C-allele and significant differences in rs2010963, rs833068, and rs3025020 genotype distribution were seen in VOC than steady-state patients. Increased VOC risk was seen with rs2010963 as heterozygous and more as homozygous, and in rs833068 and rs3025020 homozygous carriers. While there were no differences in VEGF levels between VOC and steady-state controls, there was a progressive decline in serum VEGF in rs2010963 and rs833068 heterozygous and homozygous genotypes, but an opposite trend was seen in VOC patients. Haploview analysis revealed high LD between rs699947, rs833061, rs1570360, rs2010963, rs833068, and rs833070, but weak or no LD between rs3025020 and rs3025039 and other SNPs. Six-locus (rs699947/rs833061/rs1570360/rs2010963/rs833068/rs833070) VEGFA haplotype analysis identified haplotype 111111 to be negatively (OR = 0.68) and haplotype 111222 to be positively (OR = 1.89) associated with VOC. rs2010963, rs833068, and rs3025020 were correlated with VOC type, while rs3025020 was correlated with hospitalization, VOC treatment, and duration. Specific VEGFA variants contribute to the pathogenesis of SCD VOC.

Vascular endothelial growth factor A genetic polymorphisms and AMD in Tunisians

AbstractPurpose To determine whether vascular endothelial growth factor (VEGF) gene polymorphism plays a role in either susceptibility risk for exudative AMD, serum VEGF levels variations and treatment with intravitreal bevacizumab in TunisiansMethods In this case–control study, we included 96 patients with exudative AMD and 207 age‐matched controls treated with intravitreal bevacizumab. Single nucleotide polymorphism (SNP) genotyping was performed using restriction fragment length polymorphism (RFLP) analysis of polymerase chain reaction (PCR) products. The serum VEGF was assayed by ELISA (R&amp;D).Results The frequency of the VEGF ‐2578 A allele was significantly higher in AMD patients than in controls (p=0.005; OR: 2.12[1.23‐3.66]) and was statistically associated to higher serum levels of VEGF (93.30 pg/ml versus 39.75 pg/ml for C allele) (p: 0.021). When examining the effect of this polymorphism on post‐treatment visual acuities (VA), we observed that A variant allele was also statistically more prevalent among patients with better outcome for distance and reading visual acuity after three bevacizumab injections compared to those with loss of 3 or more lines in visual acuity (OR = 2.5, 95% CI [1.13‐5.73], p = 0.02). Furthermore, the mean of VEGF plasma level is significantly higher (170.97 pg/ml) in patients with enhanced VA compared to those with worse outcome for distance and reading visual acuity (45.52pg/ml) (p=0.003).Conclusion In addition to the higher risk for exudative AMD in Tunisian patients with the ‐2578 A VEGF, our results show that this allelic variant also correlates with better visual acuity outcome after treatment with bevacizumab probably through a functional or quantitative variation of plasma levels of this molecule.

Methodological remarks concerning the recent meta-analysis on vascular endothelial growth factor polymorphism and endometriosis risk

We read with great interest the recent meta-analysis by Liang et al. [1], which evaluated the association between vascular endothelial growth factor (VEGF) gene polymorphisms and endometriosis risk. Eleven studies were included in their meta-analysis and their study found that the VEGF ?936 C/T gene polymorphism is a risk factor for endometriosis, and not -460T/C, ?405G/C, -2578A/C, -1154G/A. Nevertheless, close inspection of the study revealed some methodological issues that are worth mentioning and clarifying. The major issue of this meta-analysis is the lack of subgroup analysis, which may make the results untrustworthy. For the ?936 C/T; -460T/C and ?405G/C polymorphisms, there were enough studies for subgroup analysis. The most obvious differences among the included studies were the ethnicity that the included patients in the original studies came from. For example, some studies in this meta-analysis were based on Asian populations, while the other studies were based on Caucasian patients. As previously described, ethnicity can strongly influence the distribution of gene polymorphisms [2]. Therefore, it is essential to perform the subgroup analysis by ethnicity in meta-analysis of Liang et al. [1]. For the VEGF ?936 C/T polymorphism, Liang et al. [1] found that it was associated with an increased endometriosis risk. However, when stratifying for ethnicity, there was no significant association between VEGF gene ?936 C/T polymorphism and endometriosis among Asians (TT ? TC vs. CC: OR = 1.20, 95 % CI 0.92–1.55, P = 0.18, TC vs. CC: OR 1.18, 95 % CI 0.90–1.54, P = 0.23) and Caucasians (TT ? TC vs. CC: OR = 1.18, 95 % CI 0.99–1.40, P = 0.06, TC vs. CC: OR 1.19, 95 % CI 1.00–1.42, P = 0.05). For the VEGF ?405G/C polymorphism, Liang et al. [1] did not detect any association in any comparison model. However, when stratifying for ethnicity, a significantly decreased association was observed between VEGF ?405G/C polymorphism and endometriosis among Asians (CC ? GC vs. GG: OR = 0.74, 95 % CI 0.59–0.93, P = 0.009, GC vs. GG: OR 0.76, 95 % CI 0.60–0.97, P = 0.03), while a significantly increased association was found between VEGF ?405G/C polymorphism and endometriosis among Caucasians (CC ? GC vs. GG: OR = 1.17, 95 % CI 1.00–1.37, P = 0.04). Moreover, close inspection of the data provided by the authors (Table 1 in the meta-analysis) revealed an issue that is worth mentioning. The data reported by Liang et al. for the study of Altinkaya et al. [3]. about VEGF ?405G/C polymorphism do not seem to be in line with the data provided by Altinkaya et al. [3] in their original publication. The numbers reported by Liang et al. for CC, CG, GG, in cases for Altinkaya et al. [3], were 22-57-16, while the numbers for CC, CG, GG, in cases were 25-57-16 in Altinkaya et al.’s [3] original study. In conclusion, this letter points out interesting methodological aspects concerning the subgroup analysis by race; and it would be valuable if the authors could take into account this remark.

Vascular Endothelial Growth Factor Gene Polymorphisms and Choroidal Neovascularization in Highly Myopic Eyes

To investigate a potential association between VEGF gene polymorphisms and the occurrence and/or the size of choroidal neovascularization (CNV) in highly myopic eyes. In the case-control study for CNV occurrence, 327 highly myopic Japanese patients were enrolled. One hundred and eighty-four patients had CNV in at least one eye, and 143 did not have CNV in either eye. Of the 184 patients with CNV, 83 patients were used to evaluate an association with CNV size, and an additional 76 patients with CNV were used to confirm the association. We genotyped four tag single nucleotide polymorphisms (SNPs) and four functional SNPs previously reported to be correlated with VEGF gene expression to evaluate the associations of these eight SNPs with CNV occurrence and size. To confirm the association between CNV size and VEGF gene polymorphism, the associated SNP was genotyped in 76 additional patients with myopic CNV. There was no significant association between the occurrence of myopic CNV and the SNPs in the VEGF gene (P > 0.16). Of the eight SNPs evaluated, however, rs2010963 showed significant association with CNV area (P = 0.0047). This association was successfully replicated in the additional 76 eyes with myopic CNV, and pooled analysis revealed significant association of rs2010963 with CNV size (P = 0.00078). VEGF gene polymorphisms were not associated with CNV occurrence in highly myopic eyes but were significantly associated with the size of CNV, suggesting roles in the growth rather than the emergence of CNV.

Abstract 4539: Vascular endothelial growth factor gene polymorphisms and clinical outcome in advanced gastric cancer treated with FOLFOX

Abstract Background: Single-nucleotide polymorphisms (SNPs) of the vascular endothelial growth factor (VEGF) gene may have an impact on tumor progression, and response to chemotherapy. The aim of this study is to evaluate the associations between VEGF SNPs and clinical outcome in advanced gastric cancer patients treated with oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX). Methods: One hundred ninety recurrent or metastatic gastric cancer patients were enrolled in this study and treated with FOLFOX regimen. Genomic DNA was isolated from whole blood, and six VEGF (-2578C/A, –2489C/T, –1498T/C, –634G/C, 936C/T, and 1612G/A) gene polymorphisms were analyzed by PCR. Results: Patients genotyped G/G for –634G/C gene polymorphism had lower response rate (22.2%) than those G/C or C/C (32.3%, 51.1%; p = 0.034). The median serum levels of VEGF was higher in G/G genotypes than G/C + C/C (724.1 pg/ml vs. 462.4 pg/ml, p = 0.041). Patients with the VEGF –634CG/C polymorphism G/C + C/C genotype had a longer time to progression (TTP) of 4.9 months, compared with the TTP of 3.5 months for those with the G/G (p = 0.012, log-rank test). By multivariate analysis, this G/G genotype of –634G/C polymorphism was identified as an independent prognostic factor (Hazard ratio 1.497, p = 0.017). No significant influence on overall survival (OS) was observed by the –634 G/C. However, other SNPs were not related to response rate, TTP, or OS. Conclusion: Our data suggest that G/G genotype of –634G/C polymorphism is related to the higher serum levels of VEGF, and poor clinical outcome in advanced gastric cancer patients. It may help to identify patients who are more sensitive to FOLFOX regimen. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4539. doi:1538-7445.AM2012-4539

Identification of specific vascular endothelial growth factor susceptible and protective haplotypes associated with recurrent spontaneous miscarriages

We investigated the association of vascular endothelial growth factor (VEGF) gene polymorphism with recurrent spontaneous miscarriage (RSM). VEGF -2578C/A, -1154G/A, -634G/C, +936C/T single nucleotide polymorphisms (SNPs) were assessed in 304 RSM patients, and 371 age-and body mass index-matched control subjects using real-time PCR. Higher minor allele frequency of -1154G/A (P < 0.001) and +936C/T (P < 0.001), but not -2578C/A (P = 0.55) or -634G/C (P = 0.87) SNPs, were seen in patients. Significant differences in the distribution of -1154G/A (P = 0.006) and +936C/T (P = 0.015), but not -2578C/A (P = 0.473) or -634G/C (P = 1.000) genotypes, were seen in cases compared with control women. Of the possible 16 VEGF haplotypes, 9 were found to be common, and were included. A significantly lower frequency of C G C C (P = 0.008), and A G G C (P < 0.001) haplotypes, and a higher frequency C G C T (P = 0.020), and C G T (P = 0.004) haplotypes were seen in patients. These results strongly support that VEGF polymorphisms, in particular-1154G/A and +936C/T, are significantly associated with RSM. Our results confirm, in the largest sample to date, previous works in other populations on VEGF polymorphism in RSM.

Vascular endothelial growth factor gene polymorphisms and endometriosis risk: a meta-analysis

The vascular endothelial growth factor (VEGF) gene polymorphism has been reported to be associated with endometriosis risk. The purpose of the present study was to perform a comprehensive meta-analysis to explore whether VEGF gene polymorphisms confer risk to endometriosis. By searching PubMed and EMBASE databases, a total of 11 studies were identified. Crude odds ratio (OR) and their corresponding 95% confidence intervals (CI) for VEGF gene polymorphisms and endometriosis risk were calculated. An association of VEGF gene +936TC polymorphism with endometriosis was found (Fixed-effect model: TT + TC vs. CC: OR 1.184, 95% CI 1.027-1.366, P = 0.020; TC vs. CC: OR 1.187, 95% CI 1.024-1.375, P = 0.023. Random-effect model: TT + TC vs. CC: OR 1.203, 95% CI 1.003-1.443, P = 0.046; TC vs. CC: OR 1.188, 95% CI 1.021-1.382, P = 0.026). No association between VEGF genes -460CT, +405CG, -2578AC, -1154GA polymorphisms and endometriosis was observed. Our results indicate that VEGF +936TC gene polymorphism is a risk factor for endometriosis, and not -460CT, +405CG, -2578AC, -1154GA.

Vascular endothelial growth factor gene polymorphisms and the risk of endometriosis: a systematic review

To analyze the potential association between the single nucleotide polymorphisms (SNP) of the vascular endothelial growth factor (VEGF) gene with the risk of endometriosis by meta-analysis. Published case-control studies about the influence of VEGF polymorphisms on endometriosis were searched and screened in Medline, the Cochrane library, China National Knowledge Internet (CNKI), Chinese Biological Medicine Disk (CBM), data base of Wanfang and Foreign Medical Journal Full-Text Service (FMJS). RevMan 5.0 software was used for meta-analysis. Finally, there were 9 literatures including 1610 endometrisis patients and 1643 controls cases, which were eligible for the criteria to investigating the VEGF SNP about -460C/T, +405C/G and +936C/T. The results of meta-analysis showed that there was no evidence for association between endometriosis and the VEGF -460C/T SNP in the genotype or allele frequencies distribution (P > 0.05). Significant differences were found between the frequencies distribution of VEGF +405CC genotype (P = 0.009, OR = 1.45, 95%CI: 1.10 - 1.91) and +405C allele (P = 0.020, OR = 1.19, 95%CI: 1.03 - 1.38), also between the +936CC genotype (P = 0.050, OR = 0.81, 95%CI: 0.66 - 1.00) and +936T allele (P = 0.040, OR = 1.20, 95%CI: 1.01 - 1.43). The VEGF +405C/G and +936C/T SNP may be associated with the risk of endometriosis. Women carrying the +405C or the +936T allele could significantly increase the risk of developing endometriosis.

Vascular endothelial growth factor gene polymorphisms in North Indian patients with end stage renal disease

ContextVascular endothelial growth factor (VEGF) is involved in the development and differentiation of the vascular system. VEGF is expressed constitutively by epithelial cells from embryonic to adult kidneys and may play a key role in progression of kidney diseases. It is required for the growth and proliferation of glomerular and peritubular endothelial cells. In the kidney VEGF expression is prominently found in glomerular podocytes and in tubular epithelial cells, while VEGF receptors are mainly seen on preglomerular, glomerular, and peritubular endothelial cells. ObjectivesWe have investigated the role of VEGF gene polymorphisms (−2578C/A,−2549 18bp I/D, −1154 G/A and +936 C/T) as a susceptibility marker for end stage renal disease (ESRD). Participants and methodsWe genotyped VEGF gene polymorphism in three hundred patients and three hundred and fifty ethnically matched unrelated healthy controls free from any renal disease. These markers were studied using ARMS-PCR and PCR-RFLP methods. Patients were categorized on the basis of the histo-pathological subtypes into chronic glomerulonephritis (CGN=109), hypertensive nephrosclerosis (HTN=106) and chronic interstitial nephritis (CIN=60). ResultsVEGF −2578C and −2549D alleles were found to be ESRD causative alleles. It was observed that there was significant differences in the frequencies of the T allele of +936C/T polymorphism among CGN, HTN and CIN respectively. VEGF −1154AA genotype and A allele were associated significantly with CGN. T–G–A–D, T–A–C–I,C–G–A–D,C–A–C–D,C–G–C–I,C–A–A–D and T–G–C–D were seven haplotypes concurred in all the ESRD patients irrespective of underlying disease. While C–G–C–D & C–G–A–I haplotypes showed risk association in CGN & CIN, C–A–C–I was observed to play predisposing role in HTN. ConclusionThe results highlight the role of studied VEGF polymorphisms in end stage renal disease at large and subsequently in the three primary kidney diseases among the North Indian population.

Vascular endothelial growth factor (VEGF) gene polymorphisms may influence the efficacy of thalidomide in multiple myeloma

Vascular endothelial growth factor (VEGF) is a potent proangiogenic factor. Several single nucleotide polymorphisms (SNPs) in the VEGF gene with influence on VEGF expression have been described. In multiple myeloma, VEGF stimulates angiogenesis which is correlated with disease progression and prognosis. In this study, we evaluated the association between genetic variations in the VEGF gene in patients with multiple myeloma and time to treatment failure (TTF) after high-dose melphalan and stem cell support (HDT), overall survival (OS) and efficacy of the anti-angiogenic drug thalidomide. Retrospectively, the SNPs -2,578C>A (rs699947), -460C>T (rs833061), +405G>C (rs2010963) and +936C>T (rs3025039) in the VEGF gene were examined in 348 patients with newly diagnosed multiple myeloma initially treated with HDT, where 176 patients were treated with thalidomide at relapse. None of the examined geno- or haplotypes was associated with differences in TTF after initial therapy or OS. A possible relation between the haplotype -2,578A/-460C/+405G (ACG) and effect of thalidomide was seen. Patients with no copies of the haplotype ACG had a longer time to next treatment than patients with one or two copies of the haplotype ACG, median 13.7 months vs. 9.2 months, p=0.007. In conclusion, the haplotype ACG in the VEGF gene may influence the efficacy of thalidomide in multiple myeloma. Further analyses are needed to confirm these findings and get insight into the functional effect of these polymorphisms, so in the future we may be able to select multiple myeloma patients who especially will benefit from treatment with thalidomide.

Vascular Endothelial Growth Factor Gene Polymorphisms in Spontaneously Aborted Fetuses

The VEGF-1154G>A polymorphism has been reported to be a genetic risk factor for recurrent spontaneous abortion in various studies; however, these studies have focused on genetic analyses of pregnant women rather than aborted fetuses. To evaluate and confirm the association between the VEGF-1154G>A polymorphism and spontaneous abortion, we focused on the relationship between four polymorphisms in the VEGF gene (-2578C>A, -1154G>A, -634G>C, and 936C>T) and spontaneously aborted fetuses (SAFs). The subjects included 118 SAFs at <20 weeks gestation and 380 normal controls consisting of children and adults. The polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis. Spontaneously aborted fetuses exhibited significantly different frequencies of the -2578CA+AA/-634CC and -1154GA+AA/-634CC combined genotypes compared with control subjects. The frequency of the -2578A/-1154A/-634C/936C haplotype was significantly higher in SAFs. VEGF genes -2578CA+AA/-634CC and -1154GA+AA/-634CC in the fetus are possible risk factors for spontaneous abortion.

Vascular endothelial growth factor gene polymorphisms in Korean patients with premature ovarian failure

ObjectiveTo study the association of vascular endothelial growth factor (VEGF) polymorphisms (−2578C>A, −1154G>A, −634G>C, and 936C>T) with premature ovarian failure (POF) in Korean patients. Study designProspective case–control study. One hundred and thirty five patients with POF and confirmed serum follicle-stimulating hormone levels of >40IU/L before the age of 40 years and 120 healthy controls with at least one live birth, regular menstrual cycles, and karyotype 46, XX. ResultsPOF patients exhibited significantly different frequencies of the VEGF −1154GA genotype (odds ratio [OR], 2.002; 95% confidence interval [CI], 1.116–3.592; P=0.019), and −2578CA+AA/−1154GA+AA combination genotype (OR, 1.805; 95% CI, 1.013–3.217; P=0.044) compared to the control group. The frequency of the −2578A/−1154A haplotype (OR, 1.647; 95% CI, 1.017–2.677; P=0.041) was significantly higher in the POF group than in the control group. ConclusionThe VEGF −1154G>A mutation, −2578CA+AA/−1154GA+AA combination genotype, and −2578A/−1154A haplotype are significantly associated with POF in Korean women.

P.1.a.007 Epistatic interaction of vascular endothelial growth factor (VEGF) and TNF-alpha gene polymorphisms is associated with major depressive disorder

P.1.a.007 Epistatic interaction of vascular endothelial growth factor (VEGF) and TNF-alpha gene polymorphisms is associated with major depressive disorder

Relation between heterozygote state of vascular endothelial growth factor (VEGF) gene polymorphism and bone mineral density

Relation between heterozygote state of vascular endothelial growth factor (VEGF) gene polymorphism and bone mineral density