Association of vascular endothelial growth factor gene polymorphisms with susceptibility and clinicopathologic characteristics of colorectal cancer

Since vascular endothelial growth factor (VEGF) is known to be a potent pro-angiogenic factor, we evaluated the potential association of two VEGF gene polymorphisms (-634G>C and 936C>T) with the susceptibility and the clinicopathologic characteristics of colorectal cancer (CRC). The VEGF genotypes were determined using fresh colorectal tissue from 465 patients who had undergone a surgical resection and peripheral blood lymphocytes from 413 healthy controls by PCR/DHPLC assay. For the -634G>C polymorphism, the -634 GC or CC genotype was associated with a decreased risk of CRC (odds ratio [OR], 0.62; p=0.001) as a dominant model of C allele, whereas the 936 TT genotype correlated with advanced stage/ metastasis, a high serum level of CA19-9, and an higher grade in patients with CRC. In the haplotype analyses, haplotype -634C/936C and -634G/936T were associated with a decreased susceptibility of CRC (OR, 0.53 and 0.56; p<0.001, respectively). These observations imply that the VEGF gene polymorphisms may be associated with the susceptibility or clinicopathologic features of CRC. However, further studies of other VEGF sequence variants and their biological functions are needed to understand the role of the VEGF gene polymorphisms in the development and progression of CRC.     

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.     

Lack of Association of the Vascular Endothelial Growth Factor Gene Polymorphisms with Kawasaki Disease in Taiwanese Children

INTRODUCTION: Kawasaki disease (KD) is an acute febrile vasculitis of unknown etiology that mainly occurs in infants and children. Clinical and histopathologic findings suggest that vascular endothelial growth factor (VEGF) is involved in the coronary artery lesions (CALs) development in KD. This study hypothesized that specific VEGF gene polymorphisms and their haplotypes are associated with KD susceptibility and CAL development in Taiwanese children. SUBJECTS AND METHODS: The VEGF -2578 A/C, -634 G/C, and +936 C/T single-nucleotide polymorphisms (SNPs) were genotyped in 156 children with KD and 672 ethnically matched healthy controls using the Pre-Developed TaqMan Allelic Discrimination Assay. RESULTS: No significant differences in genotype, allele, carrier, and haplotype frequencies of the three SNPs were found between healthy controls and children with KD or between patients with and without CAL. CONCLUSION: Our data suggest that VEGF -2578 A/C, -634 G/C, and +936 C/T SNPs do not confer increased susceptibility to KD or to CAL development.     

Association between VEGF polymorphisms (936c/t, -460t/c and -634g/c) with haplotypes and coronary heart disease susceptibility

Aim: Our aim was to investigate the association between single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor (VEGF) and coronary heart disease (CHD) susceptibility in Chinese Han population. Methods: 144 CHD patients and 150 healthy individuals were enrolled in the study. Three SNPs (936C/T, -460T/C and -634G/C) of VEGF were chose and then were genotyped with Sequenom time-of-flight mass spectrometry (TOFMS). Odds ratio (OR) with 95% confidence interval (CI) were used to evaluate the association of genotypes and haplotypes and CHD susceptibility. Results: The frequencies of -460T/C CC genotype (13.6%) was found higher in the case group than that of control group (6.7%), which indicated that CC genotype was a risk factor for CHD (OR=2.50, 95% CI=1.10-5.68). Correspondently, the C allele appeared to increase the risk of CHD (OR=1.54, 95% CI=1.07-2.22). For -634G/C polymorphism, the risk of the CC genotype carrier for CHD increased 2.24 fold compared to the wild genotype. Moreover, -634G/CC allele was significantly associated with CHD susceptibility (OR=1.65, 95% CI=1.15-2.36). In addition, +936C/T CT genotype and C allele appeared to be a genetic-susceptibility factors for CHD (OR=2.43, 95% CI=1.44-4.10; OR=1.95, 95% CI=1.26-3.02). The haplotype analysis showed that T-C-T, C-C-C and C-G-C haplotypes all could increase the risk for CHD (OR: 2.43, 2.77 and 2.33). Conclusion: we concluded VEGF polymorphisms were associated with CHD susceptibility. Moreover, the haplotypes of T-C-T, C-C-C and C-G-C all could increase the risk for CHD.     

Vascular endothelial growth factor gene polymorphisms are associated with the risk of developing adenomyosis

Vascular endothelial growth factor (VEGF), a major mediator of angiogenesis and vascular permeability, may play a key role in the development of adenomyosis. The aim of this study was to investigate whether these four VEGF polymorphisms (?2578C/A, ?1154G/A, ?460C/T, and +936C/T) were associated with the risk of adenomyosis development. Genotypes were determined by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) assay in 174 adenomyosis patients and 199 frequency‐matched control women. There were significant differences between patients and control group in allele frequencies and genotype distributions of the ?2578C/A polymorphisms (P = 0.010 and 0.044, respectively). Compared with the C/C genotype, the A/A + C/A genotype could significantly modify the risk of developing adenomyosis [odds ratio (OR) = 0.64, 95% confidence interval (CI) = 0.42–0.97]. For the ?1154G/A polymorphism, the allele frequencies and genotype distributions in patient group were significant different from those of the controls (P = 0.001 and 0.007, respectively). Compared with the G/G genotype, the A/A + G/A genotype could significantly decrease the risk of developing adenomyosis (OR = 0.51, 95% CI = 0.33–0.80). However, the genotype distributions and allele frequencies of the ?460C/T and +936C/T polymorphisms did not significantly differ between controls and patients (all P value > 0.05). The haplotype analysis suggested that the TGA (VEGF ?460/?1154/?2578) and CGA haplotypes exhibited a significant decrease in the risk of developing adenomyosis compared with the haplotype of TGC (OR = 0.64, 95% CI = 0.41–1.00; OR = 0.44, 95% CI = 0.21–0.93, respectively). The study indicated that the ?2578A or ?1154A allele of VEGF gene could significantly decrease the risk of adenomyosis and might be potentially protective factors for adenomyosis development. Environ. Mol. Mutagen., 2009. © 2009 Wiley‐Liss, Inc.     

Vascular endothelial growth factor gene polymorphisms and pre-eclampsia

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

Vascular endothelial growth factor gene polymorphisms in spontaneously aborted fetuses

Citation Jeon YJ, Kim JH, Rah HC, Kim SY, Yoon TK, Choi DH, Cha SH, Shim SH, Kim NK. Vascular endothelial growth factor gene polymorphisms in spontaneously aborted fetuses. Am J Reprod Immunol 2011; 66: 544–553 Problems 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). Method of study 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. Results 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. Conclusions 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 and vasculitis susceptibility: A meta-analysis

Objective

The aim of this study was to explore whether vascular endothelial growth factor (VEGF) polymorphisms are associated with susceptibility to vasculitis.

Methods

Meta-analyses were conducted on the associations between the −634 C/G, +936 C/T, −1154 A/G, and −2578 A/C polymorphisms of VEGF and vasculitis.

Results

Eight studies on VEGF polymorphisms and vasculitis involving 2740 subjects (vasculitis 834, controls 1906) were included in this meta-analysis. The meta-analysis showed no association between vasculitis and the VEGF −634 C allele (OR = 1.161, 95% CI = 0.921–1.464, p = 0.207) among study subjects. Meta-analysis showed no association between vasculitis and the VEGF + 936 T allele (OR = 1.121, 95% CI = 0.905–1.390, p = 0.295). However, stratification by ethnicity indicated a significant association between the VEGF + 936 T allele and vasculitis in Europeans, but not in Asians (OR = 1.486, 95% CI = 1.038–2.128, p = 0.030; OR = 0.958, 95% CI = 0.773–1.253, p = 0.755). Meta-analysis showed no association between vasculitis and the VEGF −1154 A/G and 2578 A/C polymorphisms.

Conclusions

This meta-analysis suggests that the VEGF + 936 T allele is associated with susceptibility to vasculitis in Europeans, but not in Asians.     

VEGF polymorphisms and serum VEGF levels in Parkinson's disease

Accumulated data within the recent years demonstrate that reduced levels of VEGF which is a well known angiogenic molecule might cause neurodegeneration in part by impairing neural tissue perfusion, vasoregulation and normal functioning of perivascular autonomic nerves. Additionally, VEGF has been reported to support neuroprotection in dopaminergic neurons by indirect and direct mechanisms and suppress apoptosis in dopaminergic neurons in vitro. The aim of the current study is first to demonstrate whether there is an association between the three common VEGF polymorphisms (−2578C/A, −634C/G and 936C/T) in the VEGF gene and idiopathic Parkinson's disease (IPD) which is a neurodegenerative disease caused by the progressive degeneration of nigrostriatal dopaminergic neurons, and second to see if the serum levels of VEGF is reduced in the patients with IPD. We screened the genotype and allele frequencies of three common functional polymorphisms of VEGF, namely −2578C/A, −634C/G and 936C/T in DNA samples of 126 patients with IPD and healthy control subjects and also we compared the median serum levels of VEGF between these two groups. No association was found between the inspected VEGF polymorphisms and IPD and also no difference was found between the serum VEGF levels of both groups. The current study failed to support the hypothesis that VEGF polymorphisms and/or reduced serum VEGF levels are likely contributors to the neurodegenerative process in IPD.     

Vascular Endothelial Growth Factor Gene Polymorphisms May Predict the Risk of Acute Graft-versus-Host Disease following Allogeneic Transplantation: Preventive Effect of Vascular Endothelial Growth Factor Gene on Acute Graft-versus-Host Disease

Microvessel injury is associated with the development of graft-versus-host disease (GVHD), whereas high levels of posttransplantation vascular endothelial growth factor (VEGF) have a protective effect on severe acute GVHD (aGVHD) and transplantation-related mortality. The current study aimed to determine the impact of VEGFA gene single-nucleotide polymorphisms (SNPs) on the risk of aGVHD after allogeneic stem cell transplantation (SCT). Using polymerase chain reaction and restriction fragment length polymorphism, 4 VEGFA SNPs— -2578 C>A (rs699947), -460 T>C (rs833061), +405 G>C (rs2010963), and +936 C>T (rs3025039)—were analyzed in 98 recipients. Strong linkage disequilibrium was noted among loci -2578, -460, and +405, but not among these loci and locus +936. Accordingly, 4 haplotypes were generated based on the genotypes of -2578, -460, and +405: CTC (47.9%), CTG (26.7%), ACG (24.2%), and CCC (1.0%). The group with low VEGF production (ie, +936CT genotype and 2 copies of the ACG haplotype) had a higher incidence of aGVHD. Significant associations were found between the risk of grade 2-4 aGVHD and the +936 CT (P = .006), -2578 AA (P = .003), and -460 CC (P = .002) genotypes and the ACG haplotype (P = .003). No association between the VEGFA SNPs and chronic GVHD was observed. The VEGFA SNPs might predict a lower risk of aGVHD. Our findings suggest that VEGF may have a protective role in the pathogenesis of aGVHD.     

VEGF polymorphisms are not associated with an increased risk of developing renal cell carcinoma in Spanish population

Purpose

Vascular endothelial growth factor (VEGF) plays a central role in promoting angiogenesis and is over-expressed in renal cell cancer (RCC). Published data on the association between polymorphisms of vascular endothelial growth factor (e.g., −2578C/A [rs699947], −460T/C [rs833061], +405C/G [rs2010963], and +936C/T [rs3025039]) and the risk of renal cell carcinoma are ambiguous and controversial. The aim of this investigation was to investigate this relationship in a series of Caucasian Spanish patients.

Materials and methods

A case-control study was performed with 216 cases and 280 controls, genotyping subjects for VEGF polymorphisms using the predesigned TaqMan single nucleotide polymorphism (SNP) genotyping assay (Applied Biosystems, Foster City, CA, USA). The combined effect of the four gene polymorphisms on overall survival was studied by haplotype analysis.

Results

The overall results suggest that polymorphisms or haplotypes in the VEGF gene do not modify the risk of RCC. We were unable to replicate the association of the −460T/C (rs833061) polymorphism with renal cancer risk. Data were also gathered on clinical-pathological results, tumor size, clinical stage, histological grade, and survival.

Conclusions

According to our analysis of their contribution to prognostic factors, VEGF polymorphisms do not appear to exert a significant influence on RCC progression or prognosis. This finding might be explained by the tumor biology and pathogenesis of clear cell RCC. Additional studies with larger sample sizes are needed in different ethnic groups to further assess this association.     

Impact of VEGF polymorphisms on the severity of peripheral artery disease in diabetic patients

Objective. To determine the potential genotype vascular endothelial growth factor (VEGF) gene differences in diabetic patients with peripheral arterial disease (PAD), which might be associated with different stages of the vascular disease. Methods. A study was conducted with type 2 diabetic patients with PAD [n = 70; 32 intermittent claudication and 38 critical limb ischaemia (CLI)]. Genotyping of the VEGF gene insertion/deletion ? 2549, ? 2578 C/A and +405 G/C polymorphisms was done in both groups and correlated them with the severity of PAD. We compared serum VEGF levels in both groups. Results. There was a higher frequency of +405 CC and ? 2578 CC genotypes in claudication group [(31.3% vs. 5.4%, p = 0.01) and (37.5% vs. 15.8%, p = 0.05), respectively]. The presence of +405 GG and ? 2578 AA genotypes was more common among CLI patients [(57.8% vs. 37.5%, p = 0.01) and (42.1% vs. 18.8%, p = 0.05), respectively]. There were higher serum VEGF levels in patients with CLI (p = 0.029). Conclusions. We found preliminary evidence regarding the association between VEGF polymorphisms and different stages of PAD in diabetic patients.     

Association between vascular endothelial growth factor gene polymorphisms and age-related macular degeneration in a Polish population

The pathogenesis of age-related macular degeneration (AMD) is thought to be determined by an array of environmental and genetic factors. The association of increased expression of vascular endothelial growth factor (VEGF) with AMD, especially the wet form of AMD, was reported in several studies. The VEGF gene is highly polymorphic and some of its polymorphisms may affect its expression. In our work, we searched for an association between the −460C> (rs833061) and −634G>C (rs2010963) polymorphisms of the VEGF gene and the occurrence of AMD and its dry and wet forms. We have chosen these polymorphisms because they were shown to be significant in other studies and we previously showed their association with diabetic retinopathy. A total of 401 individuals were enrolled in this study: 136 controls, and 88 patients with dry and 177 with wet AMD. The polymorphisms were determined with DNA from peripheral blood lymphocytes by allele-specific and restriction fragment length polymorphism polymerase chain reaction. The significance of the polymorphisms was assessed by multiple logistic regression, producing odds ratios (ORs) and 95% confidence intervals (CIs). We observed a weak association (OR 2.90) between AMD occurrence and the C/T genotype of the −460C>T polymorphism. An association (OR 3.77) between the C/T genotype of the −460C>T polymorphism and the occurrence of dry AMD was observed. The T/T genotype considerably lowered the risk of dry AMD (OR 0.19). Dry AMD was associated with the C/C genotype of the −634G>C polymorphism (OR 3.68). Another weak association (OR 2.63) was found between the C/T genotype of the −460C>T polymorphism and the occurrence of wet AMD. The occurrence of AMD was correlated with the presence of the combined C/T–G/G genotype of both polymorphisms (OR 2.41), whereas the T/T–G/G and T/T–G/C genotypes exerted a protective effect against the disease (OR 0.22 and 0.48, respectively). The presence of the C/T–G/G and C/T–C/C combined genotypes increased the risk of dry AMD (OR 2.08 and 3.77, respectively), whereas the presence of the T/T–G/G and T/T–G/C genotypes decreased the risk (OR 0.15 and 0.28, respectively). In the wet form of AMD, the combined genotype C/T–G/G slightly favored the disease (OR 2.61) and the T/T–G/G genotype had a protective effect (OR 0.25). Analysis of haplotypes of both polymorphisms yielded similar results for AMD in general as well as for the dry and wet forms of the disease: the CG haplotype favored both forms of AMD, whereas the TG haplotype protected against both forms of AMD. The results obtained indicate that the −460C>T and −634G>C polymorphisms of the VEGF gene may be associated with the dry and wet forms of AMD in a Polish population.     

Vascular endothelial growth factor genotypes and haplotypes are associated with pre-eclampsia but not with gestational hypertension

Vascular endothelial growth factor (VEGF) is relevant for normalpregnancy, and abnormalities in VEGF functions are associatedwith hypertensive disorders of pregnancy. Because there arefew studies on how VEGF genetic polymorphisms affect susceptibilityto pre-eclampsia (PE), and no studies on how they affect susceptibilityto gestational hypertension (GH), we compared VEGF genotypeand haplotype distributions in normotensive and hypertensivepregnancies. Genotypes and haplotypes for VEGF polymorphisms(C-2578A, G-1154A and G-634C) were determined in 303 pregnantwomen (108 healthy pregnant, HP; 101 with GH and 94 with PE).When white and non-white pregnant women were considered together,no significant differences were found in the distributions ofVEGF genotypes or haplotypes (P > 0.05) in the three groups.However, with only white subjects, significant differences werefound in genotypes distributions for two (C-2578A and G-634C)VEGF polymorphisms (both P < 0.05) between the HP and thePE groups. Importantly, the haplotype including the variantsC-2578, G-1154 and C-634, which is associated with higher VEGFgene expression, was less common in the PE group compared withthe HP group (4% versus 16%; P = 0.0047). However, we foundno significant differences in VEGF haplotypes distributionswhen the HP and GH groups were compared (P > 0.05). Thesefindings suggest a protective effect for the ‘C-2578,G-1154 and C-634’ haplotype against the development ofPE, but no major effects of VEGF gene variants on susceptibilityto GH.     

Correlation between polymorphisms at interleukin‐6 but not at interleukin‐10 promoter and the risk of human T lymphotropic virus type I‐associated myelopathy/tropical spastic paraparesis in Brazilian individuals

HTLV‐1 is the etiologic agent of ATL and HAM/TSP. The majority of HTLV‐1‐infected individuals remain asymptomatic, indicating that the infection alone is not sufficient to cause the diseases. It has been reported that cytokine gene polymorphisms, including polymorphisms at IL‐6 and IL‐10 gene, might be important. We analyzed SNP in the promoter region of the IL‐6: ?174, ?572, ?597, and ?634 positions, and IL‐10: ?592 position to evaluate the role of these polymorphisms in the HAM/TSP pathogenesis in 133 HTLV‐1 infected individuals and in 100 healthy individuals from Salvador, Bahia, Brazil. The ?634C allele frequencies were higher among HAM/TSP patients (21.2%) than among oligosymptomatic (6.5%; P = 0.038) and asymptomatic (9.5%; P = 0.025) subjects. Similarly, the ?174G allele frequencies were higher in HAM/TSP patients than in oligosymptomatic patients (P = 0.02). Moreover, the ?634GC/?174GG genotype combination was identified at a higher frequency (38.5%) in the HAM/TSP patients than in subjects with other clinical status (8.7%; P = 0.016 for oligosymptomatic and 15.5%, P = 0.012 for asymptomatic patients). However, the multivariate logistic regression including the genotypes of the three studied loci showed that only ?634 C IL‐6 carriers remain as significant and independent TSP/HAM predictor (odds ratio [OR] = 5.31; 95% [CI] = 1.60–17.56; P = 0.006). We suggest that ?634 G C in IL‐6 could contribute to HAM/TSP development and that identification of the collective influence of several cytokine polymorphisms, their prevalence, and their interaction could help to better understand this disease. J. Med. Virol. 80:2141–2146, 2008. © 2008 Wiley‐Liss, Inc.     

Vascular endothelial growth factor +405 G/C,−460 T/C and −2578 A/C polymorphisms are not associated with insulin resistance in polycystic ovary syndrome

Insulin resistance (IR) and pancreatic β-cell dysfunction are usual comorbidities in polycystic ovary syndrome (PCOS). Vascular endothelial growth factor (VEGF) is known to play an important role in the pathogenesis of PCOS. This study examined firstly the possible association of common +405 G/C,−460 T/C and −2578 A/C polymorphisms of VEGF gene with fasting glucose, fasting insulin and the indices of IR [glucose/insulin ratio (GIR), homoeostasis model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI)] in 137 patients with PCOS. None of the studied polymorphisms were found to affect IR indices significantly. However, there was a trend towards higher HOMA in +405 G and −460 T allele carriers in comparison with homozygotes +405 CC and −460 CC, respectively. With regard to −2578 A/C polymorphism, although not significant, in −2578 C carriers HOMA was lower, and GIR was higher in comparison with −2578 AA genotype. Alteration of QUICKI between genotypes was minimal and varied from 4% to 7%. Because of the relatively small sample size, more studies with greater number of cases are necessary to confirm our observations before any statement can be made about the relationship between VEGF gene polymorphism and IR parameters in PCOS.     

Polymorphism R25P in the gene encoding transforming growth factor‐beta (TGF‐β1) is a newly identified risk factor for proliferative diabetic retinopathy

Associations of the genetic polymorphisms in the promoter region and the signal peptide sequence of the transforming growth factor‐beta (TGF‐β₁) gene with proliferative diabetic retinopathy (PDR) in patients with non‐insulin‐dependent diabetes mellitus (NIDDM) were studied. A total of 245 Caucasian subjects comprised the two groups: NIDDM patients with PDR (n = 73) and NIDDM patients without PDR (n = 172). Allele frequencies of common TGF‐β₁ polymorphisms (at positions ?988C/A, ?800G/A, ?509C/T, +869T/C (L10P), and +915G/C (R25P)) were determined by PCR‐based methodology. All polymorphisms were in strong linkage disequilibrium (P < 10^?2). Significantly higher frequencies of both the L allele and the R allele of the signal sequence polymorphisms in PDR subjects were found (after a correction for multiple comparisons, P_corr < 10^?2 and P_corr < 10^?4, respectively). Calculated odds ratios (ORs) for the LL and RR genotypes were 2.89 (95% confidence interval (CI), 1.6–5.1) and 19.73 (95% CI, 2.6?146.8), respectively. No significant differences between groups were found for the ?800G/A and ?509C/T polymorphisms. The ?988A allele was not represented in our sample. Multiple logistic regression identified age, diabetes duration, and R25P polymorphism as significant predictors (P = 0.002, P = 0.000003, and P = 0.007, respectively). The frequencies of genotype combinations of the ?800G/A, ?509C/T, L10P, and R25P TGF‐β₁ polymorphisms were significantly different between the PDR and non‐PDR groups (χ² = 37.83, df = 20, P < 10^?2). The frequency of haplotype consisting of majority alleles was found significantly associated with PDR (P < 0.03). The presented data indicate that the R25P polymorphisms in the TGF‐β₁ gene could be regarded as a strong genetic risk factor for PDR. © 2002 Wiley‐Liss, Inc.     

Association of vascular endothelial growth factor gene polymorphisms with recurrent spontaneous abortion in Chinese Han women

Citation Xing X, Yan J, Zhao Y, You L, Bian Y, Chen Z‐J. Association of vascular endothelial growth factor gene polymorphisms with recurrent spontaneous abortion in Chinese Han women. Am J Reprod Immunol 2011; 65: 521–525 Problem An association of polymorphism ?1154G/A (rs1570360) in vascular endothelial growth factor (VEGF) gene with idiopathic recurrent spontaneous abortion (RSA) has been found in Caucasians. The aim of this study was to examine the association of VEGF ?1154 with RSA in a well‐defined group of Chinese Han patients. Method of study The VEGF ?1154G/A genotype was detected by real‐time PCR with TaqMan probes. The products were also subjected to gene sequence analysis to validate the PCR results. Results The allele frequencies of VEGF ?1154G/A showed no significant difference between RSA patients and the normal controls (P = 0.183). The frequencies of VEGF ?1154G/A genotypes were not significantly different between RSA patients and the normal controls (P = 0.228). Conclusion Our study revealed that VEGF ?1154G/A polymorphism was not associated with the susceptibility to RSA in Chinese Han women.