Association between transforming growth factor-α polymorphism and ankylosing spondylitis: a meta-analysis update

Abstract

Objectives: The reported results of the relationship between genetic polymorphisms of tumor necrosis factor (TNF)-α ?238, ?308 locus and ankylosing spondylitis (AS) susceptibility are not always consistent. This article aims to perform a meta-analysis to collect all the relevant studies to date to further clarify the relationship between those genetic polymorphisms and AS.

Methods: A computer search was carried out up to September 2011 for literature pertaining to AS and TNF-α polymorphisms.

Results: Twenty-two articles were included, with 2,506 cases of AS and 3,023 normal controls. We searched for genotypes A allele vs. G allele, AA vs. GG + GA, and GA + AA vs. GG in a fixed/random-effects model. The effect summary odds ratios (ORs) and 95 % confidence intervals (CIs) were obtained, which shows there was no association between genetic polymorphisms and AS. As the heterogeneity was observed, in a subgroup analysis by ethnicity, the degree of risk of two genes with AS susceptibility was similar in populations of European and Asian origin. For the human leukocyte antigen (HLA)-B27+ population, results were not statistically significant.

Conclusion: ORs of various comparisons indicate that there is no association between TNF-α ?238, ?308 polymorphisms and AS susceptibility in the overall population and in the subgroup of Asian and non-Asian descent.     

Association between transforming growth factor-β1 and left ventricular mass and diameter in hypertensive patients

Angiotensin II influences development of left ventricular hypertrophy (LVH) by stimulating cardiomyocyte hypertrophy, fibroblast proliferation, and collagen synthesis. Because pro-fibrotic actions of angiotensin may be mediated by increased production of transforming growth factor-β₁ (TGF-β₁), we assessed whether serum TGF-β₁ levels might reflect involvement in LVH development. We analyzed relationships between left ventricular mass and levels of renin, aldosterone, and TGF-β₁ in 67 hypertensive subjects (mean age 64 ± 11.3 years) with electrocardiographic evidence of LVH. Levels were obtained after a 2-week washout of antihypertensive medications; two-dimensional echocardiography was subsequently performed. Linear regression analysis showed a correlation between TGF-β₁ and LV mass (r = 0.36, P = .002). This was apparently explained by the correlation between TGF-β₁ and left ventricular diastolic internal diameter (r = 0.42, P < .001), because no correlation between TGF-β₁ levels and LV wall thickness was found. In multivariate analysis, the correlation between TGF-β₁ and internal diameter remained significant (r = 0.39, P = .0014). There were no racial differences in levels of TGF-β₁ or left ventricular geometry, and no correlations between age, blood pressure, renin, aldosterone, and left ventricular mass or dimensions. These findings indicate that serum TGF-β₁ levels are related to left ventricular structure in hypertensive subjects, suggesting its possible involvement in the process of hypertensive left ventricular remodeling.     

Transforming growth factor-β1 gene expression in hepatocellular carcinoma: A preliminary report

Background and study aimsThe transforming growth factor (TGF)-β signalling pathway plays a dual role in hepatocarcinogenesis. It has been recognised for its role as a tumour suppressor as well as a tumour promoter depending on the cellular context.The aim of this study was to investigate the clinical significance of serum TGF-β1 level and TGF-β1 messenger RNA (mRNA) in the peripheral blood of liver cirrhosis and hepatocellular carcinoma (HCC) patients as noninvasive biomarkers in diagnosing HCC.Patients and methodsTwenty patients were allocated to each of the liver cirrhosis and HCC groups, in addition to 20 healthy volunteers. TGF-β1 gene expression in peripheral blood was quantitated using real-time polymerase chain reaction (PCR), while serum TGF-β1 was analysed using enzyme-linked immunosorbent assay (ELISA).ResultsTGF-β1 gene expression was significantly lower in HCC patients (median 0.401 (0.241–0.699) fold change) than in liver cirrhosis patients (median 0.595 (0.464–0.816)) (p = 0.042) and normal controls (median 1.00 (0.706–1.426) fold change) (p = 0.001). TGF-β1 gene expression showed significant positive correlation with serum TGF-β1 (r = 0.272, p = 0.036) and significant negative correlation with alpha-fetoprotein (AFP) (r = −0.528, p = 0.001). Receiver operating characteristic (ROC) analysis was conducted for TGF-β1 gene expression in comparison with AFP. The area under the curve for TGF-β1 gene expression was 0.688 (95% CI = 0.517–0.858) (p = 0.042) and AFP was 0.869 (95% CI = 0.761–0.976) (p = 0.001). The sensitivity and specificity of TGF-β1 gene expression were 65% and 75%, respectively, at a cutoff value of 0.462 fold change.ConclusionTGF-β1 gene expression in the peripheral blood may be used as a molecular marker for the diagnosis of HCC. Additional studies on a large-scale population are necessary to gain greater insight into the impact of TGF-β1 gene expression in the pathogenesis of HCC.     

Cardioprotective actions of transforming growth factor-β

Transforming growth factor-beta (TGF-β) has been shown to have protective effects in experimental models of myocardial, mesenteric, and cerebral ischemia-reperfusion injury. These effects are mediated by its ability to block adhesion of neutrophils to endothelium and to preserve endothelial function in terms of physiologic release of nitric oxide (NO). TGF-β also maintains the rhythmicity of cultured cardiac myocytes and blocks the suppressive effects of interleukin-1 on their beating rate by antagonizing the pathologic induction of NO synthase. These data suggest that TGF-β will be useful clinically in treatment of both reperfusion injury and inflammatory diseases of the heart.     

Promoter polymorphism of transforming growth factor-β1 gene and ulcerative colitis

AIM： To elucidate the possible difference in two promoter polymorphisms of the transforming growth factor-β1 （TGF-β1） gene （-800G 〉 A, -509C 〉 T） between ulcerative colitis （UC） patients and normal subjects.
METHODS： A total of 155 patients with established ulcerative colitis and 139 normal subjects were selected as controls. Two single nucleotide polymorphisms within the promoter region of TGF-β1 gene （-509C 〉 T and -800G 〉 A） were genotyped using PCR-RFLP. RESULTS： There was a statistically significant difference in genotype and allele frequency distributions between UC patients and controls for the -800G 〉 A polymorphism of the TGF-β1 gene （P 〈 0.05）. The frequency of the TGF-β1 gene polymorphism at position -800 showed that the AA genotype and the allele A frequencies significantly differed between the patients and healthy controls （P 〈 0.05）. At position -509, there was no statically significant difference in genotype and allele frequency between the patients and control subjects.
CONCLUSION： The results of our study indicate that there is a significant difference in both allele and genotype frequency at position -800G 〉 A of TGF-β1 gene promoter between Iranian patients with UC and normal subjects.     

Expression and significance of E-cadherin,N-cadherin,transforming growth factor-β1 and Twist in prostate cancer

Objective:To study the expression of E-cadherin,N-cadherin,TGF-|3 1 and Twist protein and investigate its significance in the occurrence and development of prostate cancer.Methods:The expression of E-cadherin,N-cadherin,TGF-β1 and Twist protein in 59 prostate cancer tissues and 21 adjacent tissues were detected by immunohistochemical SABC staining,and the correlation with clinicopathological features was analyzed.Results:Positive rates of E-cadherin,N-cadherin,TGF-β1 and Twist were 32.2%,54.2%,71.2%and 74.6%,respectively,in prostate cancer tissues and 85.7%,9.52%,19.0%and 9.52%,respectively,in cancer—adjacent tissues,with significant differences between the two groups(P0.05).The reduced expression of E-cadherin was related to the differentiation of prostate cancer tissues and PSA level,but was not associated with clinical stage,lymph node metastasis,bony metastasis and age.The increased expression of N-cadherin,TGF-β1 and Twist was related to the differentiation of prostate cancer tissues,clinical stage,lymph node metastasis,bony metastasis,but not to age.The difference in positive expression of N-cadherin and TGF-β1 was significant between PSA≤20μg/L group and PSA20μg/L group,but the positive expression of Twist was not significant between groups.The expression of E-cadherin was highly negatively correlated with that of N-cadherin and also highly negatively correlated with that of Twist The expression of TGF-β1 was correlated with those of E-cadherin,N-cadherin and Twist.Conclusions:The reduced expression of E-cadherin,abnormal expression of N-cadherin,transformation form E-cadherin to N-cadherin and the increased expression of TGF-β1 and Twist play an important role in the occurrence and development of prostate cancer.     

The TNF-α, IL-1B and IL-10 polymorphisms and risk for hepatocellular carcinoma: a meta-analysis

Objective  

TNF-α-308 G/A, TNF-α-238 G/A, IL-1B-31 T/C, IL-1B-511 C/T, and IL-10-1082 G/A polymorphisms have been reported to influence the risk for hepatocellular carcinoma (HCC) in many studies; however, the results still remains controversial and ambiguous. The aim of this study was to determine more precise estimations for the relationship between TNF-α, IL-1B, and IL-10 polymorphisms and the risk for HCC by meta-analysis.     

Association between NOD2 single nucleotide polymorphisms and Grade III–IV acute graft-versus-host disease: A meta-analysis

Abstract

Objectives

The effects of NOD2 single nucleotide polymorphisms (SNPs) on Grade III–IV acute graft-versus-host disease (aGVHD) risk are somewhat contradictory in different studies. The aim of the meta-analysis was to clarify the effects of NOD2 SNPs on the incidence of Grade III–IV aGVHD.

Methods

We searched PubMed, EMBASE, Web of SCIENCE, WanFang and Chinese National Knowledge Infrastructure (CNKI) databases to collect eligible publications. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association between NOD2 polymorphisms and Grade III–IV aGVHD risk.

Results

A total of nine studies from eight publications met the inclusion criteria and were included in this meta-analysis. Patient NOD2 SNPs were not associated with aGVHD risk. A tendency of higher risk to develop Grade III–IV aGVHD was found in patients with pairs NOD2 SNPs. Subgroup analyses showed that pairs NOD2 SNPs were associated with Grade III–IV aGVHD in the Caucasian population and in identical sibling donors (IS), but not in matched unrelated donors (MUD). In patients who received hematopoietic stem cell transplantation (HSCT) with T-cell depletion and gut decontamination, there was still an association between pairs NOD2 SNPs and Grade III–IV aGVHD risk.

Conclusions

Our meta-analysis suggests that pairs NOD2 SNPs, not patient NOD2 SNPs, may be associated with Grade III–IV aGVHD risk, especially in the Caucasian population. It is also indicated that in pairs NOD2 polymorphisms group, patients who receive HSCT from IS may experience higher risk of Grade III–IV aGVHD.     

Effect of transforming growth factor-β1 on human intrahepatic cholangiocarcinoma cell growth

INTRODUCTION Intrahepatic cholangiocarcinoma (ICC) is the second most common form of primary liver cancer after hepatocellular carcinoma. Despite advances in diagnosis and treatment, the prognosis of ICC has not yet been resolved[1-3]. When compared with …     

Association between the presence of H pylori in the liver and hepatocellular carcinoma： A meta-analysis

AIM： To evaluate the arguments for and against the possible roles of H pylori in hepatocellular carcinoma （HCC）.
METHODS： We performed a systematic review of all relevant studies published in the literature. A total of 103 clinical trials and reports were identified, but only 10 trials qualified under our selection criteria. A metaanalysis was carried out by a biostatistician according to the Cochrane Reviewers＇ Handbook recommended by The Cochrane Collaboration.
RESULTS： Nine case-control studies and one retrospective cross sectional study were included in the final analysis. Overall the prevalence of H pylori infection was 53.3% （129 of 242） in cases and 10.4% （29 of 280） in controls, and the summary odds ratio for the association of H pylori infection with the risk for HCC （using the fixed-effects model, which accounted for the homogeneity across the 10 studies） was determined to be 13.63 （95% CI, 7.90-23.49）.
CONCLUSION： Our analysis showed a positive association between F1 pylori infection and the risk of HCC, with an indication of possible publication bias and possible confounders due to study designs that showed results of less pronounced associations.     

Molecular pathogenesis of hepatocellular carcinoma: altering transforming growth factor-β signaling in hepatocarcinogenesis

Hepatocellular carcinoma (HCC) occurs subsequent to liver injury, where regenerative hepatocytes develop into a dysplastic nodule and then early HCC, supporting the multistep hepatocarcinogenesis theory. Molecular alterations such as the p53 mutation, p16 gene silencing, and AKT signaling activation are found in the late stage of HCC progression. The overexpression of some marker molecules is observed at the early stage. Transforming growth factor-β (TGF-β), a potent inhibitor of cell proliferation, is frequently overexpressed in HCC, although the role of TGF-β signaling during HCC development remains controversial. We previously reported that HCC cells show TGF-β receptor-dependent growth inhibition in response to TGF-β. Also, reduced TGF-β receptor II in HCC correlates with intrahepatic metastasis and shorter time-to-recurrence, suggesting a role of TGF-β signaling in tumor suppression. In contrast, TGF-β overexpression in HCC is known to correlate with malignant potential, suggesting a role in tumor promotion. Enhanced formation of stroma is a feature of advanced HCC, and TGF-β also promotes the proliferation of stromal fibroblasts. The microenvironment produced via tumor-stromal interactions may be the key to the modulation of the dual roles of TGF-β signaling in HCC progression.     

Effect and mechanism of cysteine-rich protein 61 on transforming growth factor-β1-activatedrenal fibroblasts

正Objective To observe the expression of cysteine-rich protein 61(Cyr61)in transforming growth factor-β1(TGF-β1)-activated renal fibroblasts(NRK-49F),and to explore its effect and mechanism.Methods(1)NRK-49F cells were activated by TGF-β1 with different concentrations(0.0,0.5,1.0,2.0,5.0μg/L).Western blotting was used to detect the expression of Cyr61protein,and CCK-8 assay was used to test the proliferative activity of NRK-49F cells.(2)NRK-49F cells with