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.     

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.     

Influence of vascular endothelial growth factor single nucleotide polymorphisms on tumour development in cutaneous malignant melanoma

Vascular endothelial growth factor (VEGF) is a potent regulator of vasculogenesis and tumour angiogenesis. We have investigated whether the VEGF -2578, -1154, +405 and +936 SNPs and associated haplotypes confer susceptibility to and/or influence prognosis in cutaneous malignant melanoma (CMM) skin cancer. A total of 152 CMM patients and 266 controls were genotyped for VEGF promoter SNPs by ARMS-PCR. Strong linkage disequilibrium between the -2578, -1154 and +405 SNPs was detected (association, rho = 0.488-0.965), but not between these SNPs and SNP +936 (association, rho = 0.004-0.130). No SNPs or three SNP haplotypes (-2578, -1154, +405) were significantly associated with CMM, although a number of non-significant trends were observed. However, the VEGF -1154 AA genotype and -2578, -1154, +405 CAC haplotype were both significantly associated with less advanced (Stage 1) disease (P = 0.03). In addition, the VEGF -1154 AA genotype was associated with thinner primary vertical growth phase tumours (P = 0.002), while VEGF -1154 GG was associated with thicker primary tumours (P = 0.02). These preliminary results indicate that VEGF genotype may influence tumour growth in CMM, possibly via the effects of differential VEGF expression on tumour angiogenesis.     

Minimal Stimulation Using Gonadotropin Combined with Clomiphene Citrate or Letrozole for Intrauterine Insemination

PurposeTo evaluate the efficacy of minimal stimulation using discretely administered gonadotropin combined with clomiphene citrate (CC) or letrozole (LTZ) for intrauterine insemination (IUI) cycles.ResultsThe clinical pregnancy rate was comparable between the CC and LTZ groups (18.3% vs. 13.0%, p=0.243). The clinical pregnancy rate also showed no significant difference among the 4 groups (21.6% vs. 16.9% vs. 11.1% vs. 12.6%, p=0.507). The multiple pregnancy rate was significantly higher in LTZ compared to CC group (37.5% vs. 8.7%, p=0.028) and in the LTZ+450 compared to CC+450 group (50% vs. 13.3%, p=0.038). Overall, there were 15 cases of ovarian hyperstimulation syndrome (OHSS), with the prevalence being significantly lower in the LTZ compared to CC group (1.5% vs. 10.3%, p=0.003). OHSS was more prevalent in the CC+450 compared to the LTZ+450 group (12.4% vs. 1.1%, p=0.002).ConclusionOur findings suggest that minimal stimulation using two alternate-day gonadotropin with LTZ decreases the development of OHSS and multiple pregnancies, while maintaining comparable pregnancy rates in IUI cycles.     

Role of VEGF gene variability in longevity: a lesson from the Italian population

Vascular endothelial growth factor (VEGF) gene polymorphisms have been associated with an increased risk of developing a wide variety of disorders from diabetes to neurodegenerative diseases suggesting functions not confined to its vascular effects originally described. Based on the VEGF protective roles undisclosed in pathological conditions, we evaluate whether VEGF variability might be a determinant also for longevity. Four polymorphisms (−2578C/A, −1190G/A, −1154G/A and −634G/C) within the VEGF gene promoter region in 490 unrelated Italian healthy subjects have been analysed. Significant changes of allele, genotype (−2578/AA versus −2578/CC: OR = 2.08, p = 0.007; −1190/AA versus −1190/GG: OR = 2.01, p = 0.011) and haplotype (AAGG: 10.4% versus 14.9%, p = 0.03) frequency distributions were observed between young/elderly (25–84 years old) and long-lived (85–99 years old) subjects. These results suggest that VEGF gene variability can be inserted among the genetic factors influencing the lifespan.     

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 (VEGF) polymorphism is associated with treatment resistant depression

Antidepressive medication and electroconvulsive therapy (ECT) increase hippocampal neurogenesis by promoting expression of trophic factors, including brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF). The aims were to test for an association between the VEGF 2578 C/A polymorphism and major depressive disorder (MDD) in two patient populations compared to controls, and the association between this polymorphism and response to serotonin selective reuptake inhibitors (SSRI) and to ECT. The first patient sample consisted of 119 subjects with treatment resistant major depressive disorder who were treated with ECT and the second of 98 depressive patients treated with SSRI. Treatment response was assessed by the Montgomery and Åsberg Depression Rating Scale (MADRS). Patients scoring <8 in post-treatment MADRS were considered remitters. There was a trend that CC genotype of VEGF 2578 C/A polymorphism was more common in ECT-treated and SSRI-treated patients than in controls (31.1%, 25.5% and 18.7% respectively; p = 0.056). The VEGF 2578 C/A polymorphism was associated with treatment resistant MDD. CC genotype was more common in ECT patients than in controls (31.1% and 18.7% respectively; p = 0.015). The VEGF 2578 C/A polymorphism was not associated with treatment response to SSRI or to ECT. The finding suggests an association between VEGF 2578 C/A polymorphism and treatment resistant depression which is reported for the first time. Further studies with larger samples will be required to confirm the results.     

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.     

−1154G/A and −2578C/A polymorphisms of the vascular endothelial growth factor gene in Tunisian Alzheimer patients in relation to β-amyloid (1–42) and total tau protein

Recent evidences indicate that polymorphisms within the promoter region of the vascular endothelial growth factor (VEGF) gene may elevate the risk for Alzheimer's disease (AD). To further investigate, we have analyzed association between promoter polymorphisms of the VEGF gene in 93 AD patients and age and sex matched 113 controls from Tunisian population. The distribution of genotype and allele frequencies of the VEGF (−2578C/A) and (−1154G/A) polymorphisms did not differ significantly between AD and control groups (p > 0.05). In the subgroup of ApoE ?4 carriers, the −2578A was observed to be significantly higher in the AD patients than in the control individuals. After adjusting the data by gender, age and the ApoE ?4 status using logistic regression, the −2578A allele was found to increase the risk for sporadic AD by 1.7-fold. The present study provides the evidence that the −2578A allele may be associated with the development of AD in the individuals with ApoE ?4 allele. In addition, AD patients carrying the −2578A allele had lower Aβ42 (p = 0.029) levels than those without this allele, particularly in subjects with ApoE ?4 allele.     

Genetic polymorphisms of vascular endothelial growth factor in severe pre-eclampsia

Several lines of evidence support the hypothesis that vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of pre-eclampsia (PE). VEGF is a key component in the regulation of vascular remodelling and the survival of cytotrophoblasts in the placenta. In this case-control study, we aimed to test whether VEGF genetic polymorphisms are associated with the risk of severe PE. We enrolled 84 nulliparous pregnant women with severe PE (PE group). Their VEGF G(+405)C and VEGF C(-2578)A genotypes were determined by PCR-restriction fragment length polymorphism (PCR-RFLP) from venous blood samples and were compared with the corresponding VEGF genotypes of 96 nulliparous patients with uncomplicated pregnancies (control group). Carriers of the VEGF(+405)G allele occurred less frequently in PE than in the control group [P = 0.039; adjusted odds ratio (aOR) = 0.28, range: 0.08-0.93]. Hypertension and proteinuria were diagnosed earlier (by 1.6 weeks and 1.9 weeks, respectively) in PE patients with VEGF(-2578)A only after adjustment of this association for risk factors of PE. Our results suggest that carriers of VEGF(+405)G allele have a decreased susceptibility to PE and that the progression of PE may be modified by the presence of VEGF(-2578)A allele. Nevertheless, the clinical significance of these findings remains to be determined.     

ABCB1 Allele Polymorphism Is Associated with Virological Efficacy in Naïve HIV-Infected Patients on HAART Containing Nonboosted PIs But Not Boosted PIs

Abstract

Objective: To assess the effect of the multidrug resistance-1 single nucleotide polymorphism (ABCB1 SNP) C3435T in exon 26 on the virological responses to first-line protease inhibitor (PI)-containing HAART regimens. Method: A cohort of 182 HIV-infected patients with a PI-containing HAART regimen initiated from 1997 to 2004 was enrolled. Time to the first indetectable viral load (VL) was determined in patients with the CC, CT, or TT genotype. Results: There were 37%, 44%, and 19% of patients who had the CC, CT and TT genotypes, respectively. The median estimated times to VL indetectability in the CC, CT, and TT groups were respectively 5.9, 3.9, and 4.8 months (p = .06). In patients on a non-boosted PI regimen, ABCB1 genotype was associated with time to VL indetectability that was shorter in patients with the CT than CC genotype (CT vs. CC, hazard ratio [HR] = 0.62, p = .02; TT vs. CC, HR = 0.72, p = .21). This association was not found in patients with first-generation boosted PI-containing regimens and especially not with second-generation boosted PI-containing regimens. Conclusion: Our results show that the ABCB1 SNP in exon 26 is associated with virological efficacy in HIV-infected patients treated with non-boosted PI-containing regimens but not with those containing boosted PIs, particularly of the second generation.     

Vascular Endothelial Growth Factor Blockade Reduces Plasma Cytokines in a Murine Model of Polymicrobial Sepsis

Numerous cytokines, including vascular endothelial growth factor (VEGF), are implicated in the pathogenesis of sepsis. While overexpression of VEGF produces pulmonary capillary leak, the role of VEGF in sepsis is less clear. We investigated VEGF in sepsis, utilizing a VEGF trap (VEGF_T). Polymicrobial sepsis was induced in C57BL/6 mice by cecal ligation and puncture (CLP) and resulted in significantly increased plasma VEGF levels (234 vs. 46 pg/mL; p = 0.03). Inhibition of VEGF had no effect on mortality or lung leak but did attenuate plasma IL-6 (120 vs. 236 ng/mL; p = 0.02) and IL-10 (16 vs. 41 ng/mL; p = 0.03). These alterations in inflammatory cytokines were associated with increased levels of the dominant negative inhibitory C/EBPβ. In vitro, VEGF stimulated IL-6, IL-10 and reduced the inhibitory isoform of C/EBPβ in cultured macrophages. Together these data suggest VEGF can regulate inflammatory cytokine production in murine polymicrobial sepsis, via regulation of C/EBPβ.     

VEGF polymorphisms and severity of atherosclerosis

Introduction: Vascular endothelial growth factor (VEGF) is a potent angiogenic factor, and neovascularisation has been shown to be important in atherosclerotic plaque development. There is some disagreement as to whether VEGF acts as a pro-atherosclerotic or anti-atherosclerotic factor. In the present study we have sought to clarify this by determining genotypes and haplotypes for three reportedly functional VEGF SNPs in a large series of well documented coronary atherosclerosis patients. Methods: VEGF –2578, –1154, and –634 single nucleotide polymorphisms were genotyped in 984 subjects from the Southampton Atherosclerosis Study, using the 5'' nuclease assay for allelic discrimination (TaqMan). Results: VEGF –2578 genotypes showed a significantly different distribution in patients without myocardial infarction when stratified according to number of diseased arteries. VEGF –2578 was also associated with mean number of stenotic segments in the same patient group. The AA genotype was a risk factor and CC was protective. These associations were significant before and after adjustment for classic risk factors, and were reflected in associations between VEGF haplotypes and the number of diseased arteries and stenotic segments. As VEGF –2578 CC has been provisionally shown to be associated with higher VEGF expression than the AA genotype, these results are consistent with a protective effect for VEGF in atherosclerosis development. Some changes in VEGF –1154 genotype frequencies were also detected, but no significant associations were detected for any one particular genotype. Conclusions: This study provides preliminary evidence that VEGF polymorphism is associated with development of atherosclerosis, possibly via regulation of VEGF expression, supporting a protective effect for VEGF in atherosclerosis. These results require replication in an independent study group, combined with study of additional candidate polymorphisms in the VEGF gene.     

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.     

Interleukin-21 receptor gene polymorphism (rs2285452 A/G) is associated with susceptibility to Behçet's disease

Behçet's disease (BD) is a chronic auto inflammatory disorder of unknown aetiology. Recently, the dysregulation of interleukin-21 receptor (IL-21R) has been incriminated in different autoimmune and auto-inflammatory diseases, such as systemic lupus erythematous, rheumatoid arthritis, and type 1 diabetes. Herein, we aimed to investigate the association of two Il-21R gene polymorphisms with BD. IL-21R rs2214537 and IL-21R rs2285452 genotypings were investigated in a cohort of 110 adult patients with BD and 116 age and gender unmatched healthy controls. Genotyping was performed by mutagenically separated polymerase chain reaction with newly designed primers. IL-21R rs2285452 genotypes and alleles distribution were statistically different between patients with BD and controls. GA and AA genotypes carrying the minor A allele were more frequent in patients with BD than in healthy controls (37.3% and 11.8% vs. 23.3% and 3.4%, respectively). The minor A allele was associated with an increased BD risk (odds ratios = 2.42, 95% confidence interval = 1.214.87, p = .005). IL-21R rs2214537 GG genotype was found to be associated with susceptibility to BD in the recessive model (GG vs. CC + CG; p = .046, OR =  1.91, 95% CI =  1.003.650. IL-21R rs2285452 and IL-21R rs2214537 were not in linkage disequilibrium (D' = 0.42). The AG haplotype was more frequently observed in patients with BD than in controls (0.247 vs. 0.056, p =  .0001). This study for the first time reports the association of IL-21R rs2285452 and IL-21R rs2214537 with BD. Functional studies are required to elucidate the exact role of these genetic variants.     

Association of single nucleotide polymorphisms in TPM1 rs11071720, rs3803499, rs12148828, and rs1972041 with the risk of nonsyndromic cleft lip with or without cleft palate in a sample of the Iranian population,a preliminary report

Several lines of evidence support an association between tropomyosin 1 (TPM1) and the risk of nonsyndromic cleft lip with or without cleft palate (NSCL/P). The present study aimed to investigate the association between TPM1 polymorphisms and the risk of NSCL/P in an Iranian population. This case‐control was done on 105 NSCL/P patients and 110 unrelated healthy controls. TPM1 rs11071720, rs3803499, rs12148828, and rs1972041 polymorphisms were genotyped by the polymerase chain reaction‐restriction fragment length polymorphism method. The finding showed that rs11071720 polymorphism significantly increased the risk of NSCL/P in homozygous codominant (odds ratio [OR] = 2.54, 95% confidence interval [CI] = 1.14–5.69, p = 0.023, TT vs. CC), recessive (OR = 2.33, 95% CI = 1.06–5.18, p = 0.021, TT vs. CT + CC), and allele (OR = 1.53, 95% CI = 1.02–2.30, p = 0.030, T vs. C). The rs12148828 polymorphism was associated with protection against NSCL/P in codominant (OR = 0.27, 95% CI = 0.15–0.48, p < 0.001, TC vs. TT) and allele (OR = 0.38, 95% CI = 0.22–0.64, p < 0.001, C vs. T). Regarding rs3803499, the findings proposed that this polymorphism significantly increased the risk of NSCL/P in codominant (OR = 3.86, 95% CI = 1.19–12.56, p = 0.025, CC vs. TT) and recessive (OR = 3.74, 95% CI = 1.09–14.15, p = 0.018, CC vs. CT + TT). No significant association was practical between rs1972041 polymorphism and NSCL/P. In conclusion, the findings proposed that TPM1 polymorphisms may contribute to the etiology of NSCL/P in a sample of the Iranian population.     

Prognostic Usefulness of Metabolic Syndrome Compared with Diabetes in Korean Patients with Critical Lower Limb Ischemia Treated with Percutaneous Transluminal Angioplasty

Purpose

Metabolic syndrome (MS) is a clinical condition that shares many common characteristics with diabetes. However, unlike diabetes, the usefulness of MS as a prognostic entity in peripheral arterial disease is uncertain. This study evaluated the prognostic usefulness of MS in critical lower limb ischemia (CLI) patients.

Materials and Methods

We compared the 2-year clinical outcomes in 101 consecutive CLI patients (66±14 years; 78% men) with 118 affected limbs treated with percutaneous transluminal angioplasty (PTA) according to the presence of MS and diabetes.

Results

The number of MS patients was 53 (52%), of which 45 (85%) had diabetes. During a 2-year follow-up, the incidence of clinical outcomes, including reintervention, major amputation, minor amputation, and survival, was not significantly different between MS and non-MS patients; however, the incidence of minor amputation was significantly higher in diabetic than in non-diabetic patients (42% vs. 17%; p=0.011). Cox regression analysis for the 2-year primary patency demonstrated no association between MS and 2-year primary patency [hazard ratio (HR), 1.02; 95% confidence interval (CI), 0.45-2.30; p=0.961], whereas there was a significant association between diabetes and 2-year primary patency (HR, 2.81; 95% CI, 1.02-7.72; p=0.046). Kaplan-Meier analysis revealed no significant difference in the 2-year primary patency between MS and non-MS patients; however, the 2-year primary patency was lower in diabetic than in non-diabetic patients (p=0.038).

Conclusion

As a prognostic concept, MS might conceal the adverse impact of diabetes on the prognosis of CLI patients treated with PTA.     

Association of vascular endothelial growth factor gene polymorphisms with behcet disease in a Korean population

Vascular endothelial growth factor (VEGF) is important for angiogenesis and inflammation, both of which are codependent and contribute to the pathophysiology of Behcet disease (BD). The increased expressions of VEGF have been observed in the active stage and in the ocular inflammation of BD. Polymorphisms of the VEGF gene have been associated with chronic inflammatory disease including rheumatoid arthritis. We sought to investigate whether polymorphisms on the regulatory region of the VEGF gene are associated with susceptibility of Korean patients with BD. One hundred one native Korean patients with BD and 138 healthy unrelated controls were recruited. Genotype and allele frequencies of the four selected polymorphisms (-2578, -1154, -634, and 936) were not different between the BD group and controls. Among the BD patients, the frequency of the -634 CC genotype decreased in patients with uveitis (2.6% vs. 20.6%, adjusted OR = 0.100, 95% CI 0.011-0.875, p = 0.037), although it became insignificant after correction for multiple comparisons. These results indicate that the VEGF gene polymorphisms are not associated with BD in the Korean population, but they may be involved in the development of the ocular inflammation of BD.     

The association between interleukin-1β gene polymorphisms and the risk of breast cancer: a systematic review and meta-analysis

IntroductionIt is reported that there is a close association between interleukin-1β (IL-1β) gene polymorphisms and breast cancer risk. However, the results remain controversial.Material and methodsEligible published articles were searched in PubMed, Embase, and Web of Science databases up to June 2018. Odds ratios with 95% confidence intervals were used to identify potential links between IL-1β genetic polymorphisms and the risk of breast cancer.ResultsFrom our results, we found that three common polymorphisms in IL-1β (rs16944, rs1143634, rs1143627) had no significant associations with breast cancer risk in all genetic models. Based on the analysis from ethnic subgroups, there was a higher risk of breast cancer for rs16944 polymorphism in the recessive model and heterozygous model among Asians (TT vs. CC+CT: 1.229, 95% CI: 1.063–1.422, p = 0.005; TT vs. CT: 1.211, 95% CI: 1.057–1.388, p = 0.006). For the rs1143627 polymorphism, a significantly decreased breast cancer risk was observed in the dominant model only in Asians (CT+TT vs. CC: OR = 0.944, 95% CI: 0.897–0.994, p = 0.027). After stratifying patients according to the menopausal state, we found that polymorphism of rs1143627 correlated with reduced breast cancer risk among post-menopausal women in three genotype models: allele, recessive model and homozygous model (T vs C: 0.859, 95% CI: 0.753–0.98, p = 0.024; TT vs. CC+CT: 0.727, 95% CI: 0.576–0.918, p = 0.007; TT vs. CC: 0.743, 95% CI: 0.626–0.882, p = 0.001). As for other analyses with reference to source of controls and genotyping methods, no significant association between IL-1β polymorphism and breast cancer risk was demonstrated.ConclusionsThe rs16944 and rs1143627 polymorphisms are significantly associated with the risk of breast cancer only in Asian people and in post-menopausal women respectively.     

ORIGINAL ARTICLE: Association Study of Vascular Endothelial Growth Factor and Polymorphisms of its Gene with Ectopic Pregnancy

Citation Elito J Jr, Daher S, Fernandes da Silva MO, Marconi NMH, Pendeloski KPT, Moron AF, Camano L. Association study of vascular endothelial growth factor and polymorphisms of its gene with ectopic pregnancy. Am J Reprod Immunol 2010; 63: 120–125 Problem In ectopic pregnancy, increased levels of vascular endothelial growth factor are present. The aims of this study were to determine the association between ?634C/G, ?460T/C, and +936C/T vascular endothelial growth factor (VEGF) polymorphisms and ectopic pregnancy, and to determine whether serum levels of VEGF were affected by genetic factors. Method of study This is a case–control study wherein 74 women with a history of ectopic pregnancy in a tertiary care center were compared to 134 post‐menopausal controls with two pregnancies and no ectopic pregnancy for the genotyping of VEGF polymorphisms. For 35 patients with the diagnosis of ectopic pregnancy, serum concentrations of VEGF were obtained before the treatment. Genotyping of VEGF (?634C/G, ?460T/C, and +936C/T) polymorphisms was performed by PCR, followed by endonuclease digestion. ELISA was performed to evaluate the VEGF serum levels. Results The ?634C/G, ?460T/C, and +936C/T VEGF polymorphisms were not associated with ectopic pregnancy (P = 0.170, P = 0.285, and P = 0.700, respectively). The serum levels of VEGF were not associated with the genotype of ?634C/G, ?460T/C, and +936C/T VEGF polymorphisms (P = 0.702; P = 0.347, and P = 0.256, respectively). Conclusion There was no association between ectopic pregnancy and ?634C/G, ?460T/C, and +936C/T VEGF polymorphisms. There was no correlation between VEGF genotype and the expression of VEGF in blood samples.