Cyclin D1 G870A Polymorphism and Risk of Nasopharyngeal Carcinoma: A Case-Control Study and Meta-Analysis

Background

Cyclin D1 (CCND1) plays a key role in cell cycle regulation. It is a well-established human oncogene which is frequently amplified or overexpressed in cancers. The association between CCND1 G870A polymorphism and cancer risk has been widely assessed. However, a definitive conclusion between CCND1 G870A polymorphism and risk of nasopharyngeal carcinoma (NPC) remains elusive.

Methods

We firstly performed a hospital-based case-control study involving 165 NPC cases and 191 cancer-free controls in central-south China, and then conducted a meta-analysis with six case-control studies to evaluate the association between NPC risk and CCND1 G870A polymorphism.

Results

The case-control study found a significant association between CCND1 G870A polymorphism and NPC risk in various comparison models (AA vs. GG: OR = 2.300, 95% CI 1.089–4.857, p = 0.029; AG vs. GG: OR = 2.832, 95% CI 1.367–5.867, p = 0.005; AA/AG vs. GG: OR = 2.597, 95% CI 1.288–5.237, p = 0.008; AA vs. AG/GG: OR = 0.984, 95% CI 0.638–1.518, p = 0.944). Further meta-analysis showed that there was no significant association between CCND1 G870A polymorphism and NPC risk in overall analysis. In the stratified analysis by race, however, significant associations were only found in Caucasians (for the allele model A vs. G: OR = 0.75, 95% CI 0.59–0.97, p = 0.03; for the co-dominant model AA vs. GG: OR = 0.52, 95% CI 0.32–0.86, p = 0.01; for the dominant model AA/AG vs. GG: OR = 0.49, 95% CI 0.32–0.74, p<0.01; for the recessive model AA vs. AG/GG: OR = 0.90, 95% CI 0.61–1.34, p = 0.60).

Conclusions

A significant association between CCND1 G870A polymorphism and NPC risk was found in the central-southern Chinese population. The meta-analysis indicated that CCND1 G870A polymorphism may contribute to the development of NPC in Caucasians.     

Association between MMP-1 g.-1607dupG Polymorphism and Periodontitis Susceptibility: A Meta-Analysis

Background

Matrix metalloproteinase-1 (MMP-1) plays an important role during the destruction of periodontal tissue. Although multiple studies had focused on the association between MMP-1 g.-1607dupG and periodontitis susceptibility, the results remained inconclusive. The purpose of this meta-analysis was to explore its role in the development of periodontitis.

Methods

Retrieved studies from Pubmed, Web of Science, Medline and Google Scholar Search regarding MMP-1 g.-1607dupG and periodontitis susceptibility were included into the final analysis with definite selection and exclusion criteria. Overall and stratified analyses based on disease type, severity, ethnicity and smoking status were performed. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the association between MMP-1 g.-1607dupG and periodontitis susceptibility, while Q test and Egger’s test were adopted respectively to assess heterogeneity among studies and publication bias.

Results

A total of 1580 periodontitis cases and 1386 controls in 11 case-control studies were included in the meta-analysis. The pooled results showed significant association between periodontitis susceptibility and MMP-1 g.-1607dupG polymorphism in homozygote (2G/2G versus 1G/1G, OR = 1.50, 95% CI = 1.02–2.20) and dominant model analysis (2G/2G+2G/1G versus 1G/1G, OR = 1.28, 95% CI = 1.04–1.57). For subgroups by type of periodontitis, increased risk of chronic periodontitis was observed on heterozygote (2G/1G versus 1G/1G, OR = 2.01, 95% CI = 1.58–2.56) and dominant model (OR = 1.27, 95% CI = 1.03–1.57). Furthermore, similar association was also detected in severe chronic periodontitis (2G/2G versus 1G/1G, OR = 2.15, 95% CI = 1.35–3.43; 2G/2G+2G/1G versus 1G/1G, OR = 1.64, 95% CI = 1.12–2.39; 2G/2G versus 2G/1G+1G/1G, OR = 1.86, 95% CI = 1.31–2.64).

Conclusions

Our meta-analysis demonstrated that MMP-1 g.-1607dupG polymorphism was associated with chronic periodontitis, especially the severity of the disease condition.     

Relationship between Interleukin-10 ?1082A/G Polymorphism and Risk of Ischemic Stroke: A Meta-Analysis

Objective

To analyze the association between −1082A/G polymorphism in interleukin-10 (IL-10) gene and ischemic stroke (IS) risk by meta-analysis.

Methods

We carried out a systematic electronic search in PubMed, BIOSIS Previews, Science Direct, Chinese National Knowledge Infrastructure, Chinese Biomedical Database, Weipu database and WANGFANG Database. Pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated to assess the strength of the association.

Results

7 studies were included. There was no significant association between IL-10 −1082A/G polymorphism and IS risk under all genetic models in overall estimates (A vs. G: OR = 1.23,95%CI = 0.85–1.79;AA vs. GG: OR = 1.01,95%CI = 0.47–2.19; AG vs. GG: OR = 0.76, 95%CI = 0.38–1.55; AA+AG vs. GG: OR = 0.89,95%CI = 0.46–1.73; AA vs. AG+GG: OR = 1.39, 95%CI = 0.91–2.13). Similarly, no associations were found in subgroup analysis based on ethnicity and source of controls. However, removing the study deviating from Hardy–Weinberg equilibrium (HWE) produced statistically significant associations for overall estimates under recessive model(AA VS. AG+GG OR 1.58, 95% CI 1.04–2.42) and among Asians in all genetic models (A VS.G OR 1.64, 95% CI 1.07–2.53; AA vs. GG OR1.91, 95% CI 1.31–2.80; AG vs. GG OR1.44, 95% CI 1.09–1.91; AA+AG vs. GG OR 1.54, 95% CI 1.18–2.01;AA VS. AG+GG OR 1.79, 95% CI 1.07–3.00). Even after Bonferroni correction, the associations were observed still significantly in Asians under the two models (AA vs. GG OR1.91, 95% CI 1.31–2.80, P = 0.0008; AA+AG vs. GG OR 1.54, 95% CI 1.18–2.01, P = 0.001).

Conclusion

This meta-analysis indicates that IL10 −1082 A/G polymorphism is associated with IS susceptibility in Asians and the −1082 A allele may increase risk of IS in Asians. Considering the sample size is small and between-study heterogeneity is remarkable, more studies with subtle design are warranted in future.     

The MMP-9 -1562 C/T Polymorphism in the Presence of Metabolic Syndrome Increases the Risk of Clinical Events in Patients with Coronary Artery Disease

Background and Objectives

Elevated levels of matrix metalloproteinase (MMP)-9 have been associated with the metabolic syndrome (MetS) and cardiovascular events. The MMP-9 −1562 C/T polymorphism has furthermore been shown as a risk factor for coronary artery disease (CAD). The non-favourable cardiometabolic state in MetS may increase the risk. We aimed to investigate the influence of MMP-9 −1562 C/T polymorphism in subjects with CAD and MetS.

Methods

Patients (n = 1000) with verified CAD stratified in Mets +/− (n = 244/756), were analyzed for the MMP-9 −1562 C/T polymorphism and related to clinical events after 2 years follow-up. Serum levels of total MMP-9 and tissue inhibitor of matrix metalloproteinases (TIMP)-1were analyzed in all, whereas MMP-9 activity, extracellular matrix metalloproteinase inducer (EMMPRIN), and expression of the two genes were analyzed in a subset of 240 randomly selected patients.

Results

Totally, 106 clinical endpoints were recorded. In MetS; the T-allele associated with 5.5 fold increase in event rate (p<0.0001), increased with number of MetS components, a 117% increase in total MMP-9 levels (TT homozygous, p = 0.05), significantly higher total- and endogenous active MMP-9 and TIMP-1 levels (p<0.01 all), and EMMPRIN was inversely correlated with pro- and endogenous active MMP-9 (p<0.05, both). In non-MetS; the T-allele was not associated with new events, nor higher MMP-9 levels. EMMPRIN was significantly correlated with total MMP-9 and TIMP-1 (p<0.01, both) and the two genes were inter-correlated (p<0.001).

Conclusion

In CAD patients with MetS, the MMP-9 T-allele increased the risk of clinical events, probably mediated through elevated MMP-9 levels and altered MMP-9 regulation.     

Meta-Analysis on the Associations of TLR2 Gene Polymorphisms with Pulmonary Tuberculosis Susceptibility among Asian Populations

Background

Publications regarding the associations of toll-like receptor 2 (TLR2) G2258A and T597C polymorphisms with pulmonary tuberculosis (PTB) susceptibility are inconsistent. A meta-analysis was conducted to investigate the relationship between TLR2 G2258A and T597C polymorphisms with PTB susceptibility.

Methods

A systematic search was performed for published studies on the relationship between TLR2 polymorphisms and PTB susceptibility. Information was gathered from each eligible study, and statistically analyzed.

Results

6 eligible studies, totaling 1301 cases and 1217 controls on G2258A genotypes, and 8 studies, totaling 2175 cases and 2069 controls on T597C genotypes, were included in the analysis. TLR2 2258G allele and 2258GG genotype were found to be associated with decreased PTB susceptibility (A vs. G: OR  = 3.02, 95% CI: 2.22–4.12, P<0.001, GA+AA vs. GG: OR  = 2.69, 95% CI = 1.49–4.87, P = 0.001). In the subgroup analyses, the 2258G allele and 2258GG genotype also exhibited a protective effect of PTB risk in Asians (A vs. G: OR  = 2.95, 95% CI: 1.91–4.55, P<0.001; GA+AA vs. GG: OR  = 3.59, 95% CI: 2.23–5.78, P<0.001), while no associations were observed in Caucasians. No significant associations between T597C polymorphism and PTB were found in the allele model (C vs. T: OR  = 0.95, 95% CI: 0.86–1.04, P = 0.28), co-dominant model (CC vs. TT: OR  = 0.88, 95% CI = 0.92–1.40, P = 0.25; CT vs. TT: OR  = 0.92, 95% CI = 0.80–1.06, P = 0.28), recessive model (CC vs. TT+TC: OR  = 0.96, 95% CI: 0.80–1.16, P = 0.69), or dominant model (TC+CC vs. TT: OR  = 0.93, 95% CI = 0.76–1.15, P = 0.51). The associations of T597C polymorphism with PTB susceptibility, in the ethnic-specific analyses, were still not significant.

Conclusion

TLR2 2258G allele may provide protective effects against PTB susceptibility, particularly among Asians, whereas TLR2 T597C polymorphism might not be associated with PTB susceptibility.     

Relationship between Rad51 G135C and G172T Variants and the Susceptibility to Cancer: A Meta-Analysis Involving 54 Case-Control Studies

Background

The associations between Rad51 gene polymorphisms (G135C and G172T) and risk of cancer have been investigated, but the results were inconclusive. To get a comprehensive evaluation of the association above, we performed a meta-analysis of published studies.

Methods

A computerized search of PubMed, Embase and Web of Knowledge databases for all relevant studies was performed and the data were analyzed in a meta-analysis. The overall odds ratio (OR) with the 95% confidence interval (95% CI) was calculated to assess the strength of the association between Rad51 polymorphisms and cancer risk. Data were analyzed using fixed- or random-effects model when appropriate. Sensitivity analysis and publication bias test were also estimated.

Results

Overall, a total of 54 case-control studies were included in the current meta-analysis, among which 42 studies with 19,142 cases and 20,363 controls for RAD51 G135C polymorphism and 12 studies with 6,646 cases and 6,783 controls for G172T polymorphism. For G135C polymorphism, the pooled results indicated that significantly increased risk was found in overall cancers (homozygote model: OR = 1.776, 95% CI = 1.288–2.449; allelic genetic model: OR = 1.169, 95% CI = 1.016–1.345; recessive model: OR = 1.946, 95% CI = 1.336–2.835), especially in breast cancer (homozygote model: OR = 1.498, 95% CI = 1.026–2.189; recessive model: OR = 1.732, 95% CI  =  1.170–2.562). For G172T polymorphism, a decreased cancer risk was observed in head and neck cancer (homozygote model: OR  =  0.621, 95% CI  =  0.460–0.837; allelic genetic model: OR  =  0.824, 95% CI  =  0.716–0.948; recessive model: OR  =  0.639, 95% CI = 0.488–0.837).

Conclusions

Our results suggested that the Rad51 G135C polymorphism is a candidate for susceptibility to overall cancers, especially to breast cancer, and that the Rad51 G172T might play a protective role in the development of head and neck cancer.     

Combined Effects of TGFB1 +869 T/C and +915 G/C Polymorphisms on Acute Rejection Risk in Solid Organ Transplant Recipients: A Systematic Review and Meta-Analysis

Background

Transforming growth factor-beta 1(TGF-β1) is involved in the development of acute rejection (AR) episodes in solid organ transplant recipients; and a number of studies have been conducted to investigate the combined effects of human TGF-β1 gene (TGFB1) +869 T/C and +915 G/C polymorphisms on AR risk. However, the results obtained are inconclusive.

Methods

Eligible studies that investigated the haplotypic association between TGFB1 +869 T/C and +915 G/C polymorphisms and AR risk were comprehensively searched in the PUBMED, EMBASE, China National Knowledge Infrastructure, and Wanfang Database. Statistical analyses were performed by using STATA 12.0 and Review Manager 5.0.

Results

Fourteen eligible studies with 565 AR cases and 1219 non-AR cases were included. Overall, a significantly decreased risk was detected in patients carried with intermediate producer (IP) haplotypes (T/C G/C, T/T G/C, and C/C G/G) and/or low producer (LP) haplotypes (C/C G/C, C/C C/C, T/T C/C, and T/C C/C) compared with high producer (HP) haplotypes (T/T G/G and T/C G/G; IP vs. HP: OR = 0.75, 95% CI, 0.58–0.96, P _{heterogeneity}  = 0.238; IP/LP vs. HP: OR  = 0.77, 95% CI, 0.61–0.98, P _{heterogeneity}  = 0.144). In addition, subgroup analysis by transplant types demonstrated a similar association in patients receiving heart transplant (IP vs. HP: OR  = 0.32, 95% CI, 0.14–0.73, P _{heterogeneity}  = 0.790; IP/LP vs. HP: OR  = 0.41, 95% CI, 0.20–0.85, P _{heterogeneity}  = 0.320).

Conclusions

The current meta-analysis and systematic review indicated that recipient TGFB1 HP haplotypes were significantly associated with an increased risk for AR in solid organ transplant recipients, particularly patients receiving cardiac allograft.     

Treatment Outcome of Radiotherapy Alone versus Radiochemotherapy in IE/IIE Extranodal Nasal-Type Natural Killer/T Cell Lymphoma: A Meta-Analysis

Background

Previous studies have revealed conflicting findings concerning the efficacy of radiotherapy (RT) and radiochemotherapy (RCT) in IE/IIE extranodal nasal-type natural killer/T cell lymphoma (ENKTL). In this study, we conducted a comprehensive meta-analysis to address this issue.

Methods

We systematically searched PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), EmBase, BISOS, Clinical Trials and some Chinese databases for relevant studies, and 2 prospective and 15 retrospective studies involving a total of 1595 patients met our inclusion criteria.

Results

The meta-analysis showed no significant differences in complete remission (CR) [odds ratio (OR) 0.85, 95% confidence interval (CI) 0.42–1.72, p = 0.65], 5-year overall survival (OS) [hazard ratio (HR) 1.11, 95% CI 0.85–1.45, p = 0.43] and 5-year progression free survival (PFS) (HR 1.07, 95% CI 0.75–1.53, p = 0.70) in patients who received RT versus RCT. Furthermore, the addition of CT decreased neither systemic failure (SL) (OR 0.75, 95% CI 0.47–1.21, p = 0.24) nor locoregional failure (LF) (OR 1.17, 95% CI 0.68–2.01, p = 0. 57).

Conclusions

RCT did not have an obvious advantage over RT for treating IE/IIE ENKTL.     

Interleukin-13 ?1112 C/T Promoter Polymorphism Confers Risk for COPD: A Meta-Analysis

Background

Interleukin (IL)-13, a T-helper type 2 cytokine, plays a critical role in the development of chronic obstructive pulmonary disease (COPD). This meta-analysis was performed to assess the association of IL-13 −1112 C/T promoter polymorphism with COPD susceptibility.

Methods

Published case-control studies from Pubmed and China National Knowledge Infrastructure (CNKI) databases were retrieved. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated.

Results

Eight case-control studies in seven articles were included in this meta-analysis. Pooled effect size showed IL-13 −1112 C/T was associated with COPD susceptibility in a codominant genetic model (TT vs CT, OR: 1.82, 95% CI: 1.14–2.92 and TT vs CC, OR: 2.02, 95% CI: 1.10–3.72), indicating individuals with TT genotype had an increased risk for COPD compared with those with CT or CC genotype. According to ethnicity, results indicated IL-13 −1112 C/T was correlated with COPD susceptibility in Arabians (TT vs CT, OR: 2.94, 95% CI: 1.03–8.42 and TT vs CC, OR: 3.05, 95% CI: 1.08–8.59). Moreover, after excluding the study without Hardy-Weinberg equilibrium, the pooled results were robust and no publication bias was found in this study.

Conclusions

This meta-analysis suggests IL-13 −1112 C/T promoter polymorphism is associated with the risk of COPD in Arabians.     

The rs2233678 Polymorphism in PIN1 Promoter Region Reduced Cancer Risk: A Meta-Analysis

Background

Published evidence suggests that the rs2233678 (−842 G>C) polymorphism in the PIN1 (peptidyl-prolyl cis/trans somerase NIMA-interacting 1) promoter region may be associated with cancer risk; however, the conclusion is still inconclusive.

Methods

We conducted a meta-analysis to determine whether −842 G>C polymorphism was associated with cancer risk. Odds ratio (OR) and 95% confidence intervals (95% CI) were used to assess the strength of association. Genotype distribution data and adjusted ORs were collected to calculate the pooled ORs. Meta-regression was conducted to detect the source of heterogeneity. Publication bias was evaluated by Egger’s test and Begg’s test.

Results

A total of 11 eligible studies, including 9280 participants, were identified and analyzed. Overall, we found that carriers of the −842 C allele were associated with significantly decreased cancer risk (C vs. G, OR = 0.750, 95% CI: 0.639–0.880, P_{heterogeneity} = 0.014, estimated by genotype distribution data; CC+GC vs. GG, OR = 0.668, 95% CI: 0.594–0.751, P_{heterogeneity} = 0.638, estimated by adjusted ORs). No evidence of publication bias was observed. Meta-regression revealed that ethnicities (p = 0.021) and sample size (p = 0.02) but not sources of control (p = 0.069) were the source of heterogeneity.

Conclusion

These results suggest that the PIN1 rs2233678 (−842 G>C) polymorphism significantly reduces cancer risk.     

Meta-Analysis of RAGE Gene Polymorphism and Coronary Heart Disease Risk

Background

Recent data from human and animal studies have shown an upregulated expression of advanced glycosylation end product–specific receptor (RAGE) in human atherosclerotic plaques 1 and in retina, messangial, and aortic vessels, suggesting an important role of RAGE in the pathogenesis of atherothrombotic diseases. In the past few years, the relationship between RAGE polymorphisms (−429T/C, −374T/A, and G82S) and coronary heart disease (CHD) has been reported in various ethnic groups; however, these studies have yielded contradictory results.

Methods

PubMed, ISI web of science, EMBASE and the Chinese National Knowledge Infrastructure databases were systematically searched to identify relevant studies. Data were abstracted independently by two reviewers. A meta-analysis was performed to examine the association between RAGE polymorphisms and susceptibility to CHD. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.

Results

A total of 17 studies including 4343 patients and 5402 controls were involved in this meta-analysis. Overall, no significant results were observed for −429T/C (OR  = 1.01, 95% CI: 0.92–1.12, P  = 0.78), −374T/A (OR  = 1.11, 95% CI: 0.98–1.26, P  = 0.09) and G82S (OR  = 1.12, 95% CI: 0.86–1.45, P  = 0.41) polymorphism. In the stratified analyses according to ethnicity, sample size, CHD endpoint and Hardy-Weinberg status, no evidence of any gene-disease association was obtained.

Conclusions

This meta-analysis demonstrates that there is no association between the RAGE −429T/C, −374T/A and G82S polymorphisms and CHD.     

Association of A561C and G98T Polymorphisms in E-Selectin Gene with Coronary Artery Disease: A Meta-Analysis

Objective

E-selectin (SELE) mediates the rolling and adhesion of leukocytes on activated endothelial cells and plays a critial role in the pathogenesis of coronary artery disease (CAD). Associatons between the A561C and G98T polymorphisms of the SELE gene and CAD risk were investigated broadly, but the results were inconsistent. In the present study, we performed a meta-analysis to systematically evaluate the associations between the two polymorphisms and the risk of CAD.

Methods

Comprehensive research was conducted to identify relevant studies. The fixed or random effect model was selected based on the heterogeneity among studies, which was evaluated with Q-test and Ι². Meta-regression was used to explore the potential sources of between-study heterogeneity. Peters''s linear regression test was used to estimate the publication bias.

Results

Overall, 24 articles involving 3694 cases and 3469 controls were included. After excluding articles deviating from Hardy–Weinberg equilibrium in controls and sensitive analysis, our meta-analysis showed a significant association between the A561C ploymprphism and CAD in dominant (OR  = 1.84, 95% CI  = 1.56–2.16) and codominant (OR  = 1.74, 95% CI  = 1.49–2.03) models. As for the G98T polymorphism, significantly increased CAD risk was observed in dominant (OR  = 1.47, 95% CI  = 1.16–1.87) and codominant (OR  = 1.48, 95% CI  = 1.18–1.86) models, but after subgroup analysis, the association was not significant among Caucasians in dominant (OR  = 1.58, 95% CI  = 0.73–3.41) and codominant (OR  = 1.58, 95% CI  = 0.79–3.20) models.

Conclusions

Despite some limitations, our meta-analysis suggested that the SELE gene polymorphisms (A561C, G98T) were significantly associated with increased risk of CAD. However, after subgroup analysis no significant association was found among Caucasians for the G98T polymorphism, which may be due to the small sample size and other confounding factors. Future investigations with multicenter, large-scale, and multi-ethnic groups are needed.     

Prognostic Value of TNF-Related Apoptosis Inducing Ligand (TRAIL) in Acute Coronary Syndrome Patients

Background

Apoptosis plays an important role in the development of heart failure. The aim of the prospectively designed study was to assess whether the concentration of apoptotic markers apoptosis-stimulating fragment (Fas, CD95/APO-1) and tumor necrosis factor-related apoptosis inducing ligand (TRAIL) can predict prognosis in patients with acute coronary syndromes.

Methods

The concentrations of soluble Fas and TRAIL were determined in 295 patients with acute coronary syndromes. The status of all patients was evaluated at 6 months. The primary goal was a composite end-point of death and hospitalization for heart failure. The secondary end-points were re-MI, death alone and stroke alone.

Results

During the median follow-up of 6 months, 26 patients experienced the composite end-point. Using multivariate logistic regression, the concentration of TRAIL was the strongest significant and independent predictor of composite end-point (OR 0.11 (95% CI 0.03–0.45), p = 0.002). Low concentration was associated with poor prognosis of patients. Other significant predictors of composite end-point were serum creatinine (OR 7.7 (95% CI 1.1–54.5, p = 0.041) and complete revascularization (OR 0.19 (95% CI 0.05–0.78, p = 0.02). Independent significant predictors of death in the multivariate analysis were the concentration of TRAIL (OR 0.053 (95% CI 0.004–0.744), p = 0.029), older age (OR 1.20 (95% CI 1.02–1.41, p = 0.026) and serum creatinine (OR 15.1 (95% CI 1.56–145.2), p = 0.0193). Re-MI or stroke could not be predicted by any combination of obtained parameters.

Conclusions

Low concentrations of soluble TRAIL represent a strong predictor of a poor prognosis in patients with acute coronary syndrome. The predictive value of TRAIL concentration is independent of age, ejection fraction, index peak troponin level, concentration of BNP or serum creatinine.     

Comparison of Transverse Island Flap Onlay and Tubularized Incised-Plate Urethroplasties for Primary Proximal Hypospadias: A Systematic Review and Meta-Analysis

Purpose

This meta-analysis was conducted to compare postoperative outcomes between transverse island flap (TVIF) onlay and tubularized incised-plate (TIP) urethroplasties for primary proximal hypospadias.

Materials and Methods

A comprehensive literature search updated to 21^st May 2014 was carried out for relevant studies. After literature identification and data extraction, odds ratio (OR) with 95% confidential interval (CI) was calculated to compare postoperative complication rate between TVIF onlay and TIP. Meta-regression and subgroup analyses were applied to find potential affective factors.

Results

A total of 6 studies including 309 patients receiving TVIF onlay and 262 individuals subjected to TIP met inclusion criteria. The synthetic data suggested that TVIF onlay and TIP were comparable in terms of total complication rate (OR 0.85, 95% CI 0.56–1.30, p = 0.461), fistula (OR 0.68, 95% CI 0.38–1.21, p = 0.194), recurrent curvature (OR 1.16, 95% CI 0.43–3.12, p = 0.766), dehiscence (OR 0.95, 95% CI 0.33–2.74, p = 0.920), diverticulum (OR 1.90, 95% CI 0.53–6.78, p = 0.321), meatal stenosis (OR 0.74, 95% CI 0.20–2.77, p = 0.651) and urethral stricture (OR 1.49, 95% CI 0.41–5.50, p = 0.545), without significant heterogeneity for each comparison group. Meta-regression and subgroup analyses revealed no significant findings. One-way sensitivity analysis indicated that the results were stable. No publication bias was detected using both funnel plot and Egger’s test. Also, there were no obvious differences observed in cosmetic and functional outcomes.

Conclusions

This meta-analysis suggests that TVIF onlay and TIP urethroplasties are clinically equivalent. Given the inherent limitations of included studies, this conclusion should be interpreted with caution and wait to be confirmed by more well-designed randomized controlled trials with high quality in the future.     

Association between MMP1 -1607 1G>2G Polymorphism and Head and Neck Cancer Risk: A Meta-Analysis

Background

MMP1 is an important member of the MMP endopeptidase family that plays a critical role in the development of head and neck cancer (HNC). Several studies have investigated the association between the MMP1 -1607 1G>2G polymorphism and risk of HNC, but their results have been inconsistent. Here, we conducted a meta-analysis to further explore the role of the MMP1 -1607 1G>2G polymorphism in HNC development.

Methods

We identified all eligible studies in the electronic databases of PubMed, ISI Web of Knowledge, MEDLINE, Embase, and Google Scholar (from January 2000 to June 2012). A meta-analysis was performed to evaluate the association between the MMP1 -1607 1G>2G polymorphism and risk of HNC by calculating odds ratios (OR) and 95% confidence interval (CIs).

Results

Twelve studies were included in this meta-analysis. In overall comparison, significant associations were found using the recessive and allelic contrast models (OR, 1.38; 95% CI, 1.07–1.79 and OR, 1.27; 95% CI, 1.05–1.53, respectively), but no association was detected using the dominant model. In the stratified analyses by several variables, significant associations were observed using the recessive, dominant, and allelic contrast models in the Asian population (OR, 1.64; 95% CI, 1.29–2.08; OR, 1.39; 95% CI, 1.06–1.82; and OR, 1.41; 95% CI, 1.21–1.65, respectively), European population (OR, 0.58; 95% CI, 0.40–0.84; OR, 0.64; 95% CI, 0.44–0.92; and OR, 0.68; 95% CI, 0.54–0.85, respectively), and population-based subgroup (OR, 1.24; 95% CI,1.05–1.47; OR,1.48; 95% CI,1.04–2.12; and OR, 1.22; 95% CI, 1.07–1.38, respectively). Furthermore, significant associations were detected in oral cavity cancer and nasopharyngeal cancer under the recessive model.

Conclusion

Our results suggest that the MMP1 -1607 1G>2G polymorphism is associated with risk of HNC and that it plays different roles in Asian and European populations. Further studies with large sample size are needed to validate our findings.     

Worse Clinical Outcomes in Acute Myocardial Infarction Patients with Type 2 Diabetes Mellitus: Relevance to Impaired Endothelial Progenitor Cells Mobilization

Background

Although the clinical outcome of acute myocardial infarction (AMI) in patients with type 2 diabetes mellitus (T2DM) is well established to be worse than for non-diabetic patients, the reasons for this remain unclear. We hypothesized that this may be related to impairment of bone marrow-derived endothelial progenitor cells (EPCs) mobilization.

Methodology/Principal Findings

We observed short term bone marrow EPCs mobilization and long term clinical outcomes in 62 AMI patients with or without T2DM and investigated EPCs levels as well as bone marrow pathway changes in a rat model of diabetes after AMI. Patients with T2DM exhibited a delay (peak time diabetics vs. non-diabetics: day 7 vs. day 5) and a decrease in EPCs mobilization (diabetics vs. non-diabetics: 285±56/10⁶ mononuclear cells (MNCs) vs. 431±88/10⁶ MNCs, p<0.05) within one month after AMI. Plasma levels of VEGF and SDF-1α as well as of hsCRP were higher in T2DM patients. Over a mean of 2.26 years follow-up, T2DM patients exhibited a pronounced decrease in LVEF as well as an increase in clinical events. Glucose (HR 2.01, 95% CI 1.42–2.85, p = 0.008), first day EPC (HR 0.974, 95% CI 0.952–0.997, p = 0.02) and seven day EPCs (HR 0.966, 95% CI 0.945–0.988, p = 0.003) were independent prognostic variables for cardiovascular mortality. In a diabetic rat model of AMI, decreased circulating EPCs was accompanied by lower expression of phospho-Akt, phospho-eNOS, HIF, MMP-9 and MMP-9 activity in the bone marrow as well as impaired cardiac function, angiogenesis and increased left ventricle remodeling.

Conclusions/Significance

Bone marrow EPCs mobilization is delayed and reduced in diabetes, with impaired HIF/p-Akt/p-eNOS/MMP-9 signaling. This is likely to contribute to the deterioration in cardiac function and worsened clinical outcome seen in patients with T2DM.     

Adiponectin-11377CG Gene Polymorphism and Type 2 Diabetes Mellitus in the Chinese Population: A Meta-Analysis of 6425 Subjects

Background

Although adiponectin −11377CG gene polymorphism is implied to be associated with increased type 2 diabetes mellitus (T2DM) risk, results of individual studies are inconsistent.

Objective and Methods

A meta-analysis consisting of 12 individual studies, including a total of 6425 participants, was carried out in order to investigate the association of adiponectin −11377CG gene polymorphism with T2DM. The pooled odds ratio (OR) and its corresponding confidence interval (CI) at 95% were assessed through the random- or fixed- effect model.

Results

A significant relationship was observed between adiponectin −11377CG gene polymorphism and T2DM under allelic (OR: 1.150, 95% CI: 1.060 to 1.250, P = 0.001), recessive (OR: 1.450, 95% CI: 1.180–1.770, P = 0.0004), dominant (OR: 1.071, 95% CI: 1.013–1.131, P = 0.015), additive (OR: 1.280, 95% CI: 1.090–1.510, P = 0.002), and homozygous genetic models (OR: 1.620, 95% CI: 1.310–1.990, P<0.00001). No significant association was found between them under the heterozygous genetic model (OR: 1.640, 95% CI: 0.850–3.170, P = 0.140).

Conclusions

Adiponectin −11377CG gene polymorphism was significantly associated with T2DM risk susceptibility. G allele carriers are predisposed to T2DM risk.     

Association between TLR4 (+896A/G and +1196C/T) Polymorphisms and Gastric Cancer Risk: An Updated Meta-Analysis

Background

Toll-like receptor 4 (TLR4) is a receptor of lipopolysaccharide in the signaling transduction of gastric epithelial cell. It plays a pivotal role in activation of innate immunity and pathogen recognition and thus acts as a modulator in the development and progression of gastric cancer. Growing studies explored the association of polymorphisms in TLR4 with susceptibility to gastric cancer, but the results have remained controversial and conflicting. To investigate the effect of two selected TLR4 (+896A/G and +1196C/T) polymorphisms on gastric cancer, we performed a meta-analysis.

Methods

A comprehensive search was conducted to identify all eligible case-control publications investigating the association between TLR4 polymorphisms and gastric cancer risk. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were used to assess such association.

Results

Up to March 26 2014, 10 published case-control studies from PubMed and EMBase were available, involving a total of 1888 gastric cancer patients and 3433 control subjects. In the overall meta-analyses, a significantly increased gastric cancer risk was detected in TLR4 +896A/G polymorphism (heterozygous model, AG vs. AA: OR = 1.67, 95% CI, 1.39–2.01; additive model, G vs. A: OR = 1.64, 95% CI, 1.37–1.95) and TLR4 +1196C/T polymorphism (heterozygous model, CT vs. CC: OR = 1.42, 95% CI, 1.11–1.81; additive model, T vs. C: OR = 1.36, 95% CI, 1.08–1.72), similar results were obtained in the subgroup analyses of Caucasian, whereas no associations were detected in any genetic models of non-Caucasian.

Conclusions

The overall results suggest that TLR4 polymorphisms (+896A/G and +1196C/T) may be associated with a significantly increased gastric cancer risk in Caucasian.     

Matrix metalloproteinase-9 -1562 C/T polymorphism is associated with the risk of sepsis in a Chinese population: A retrospective study

Matrix metalloproteinase-9 (MMP-9) has been shown to participate in the pathogenesis of sepsis. In this study, we recruited 312 sepsis patients and 413 controls to explore the relationship between sepsis risk and the MMP-9 -1562 C/T polymorphism in Han Chinese. The PCR restriction fragment length polymorphism method was used for genotyping. Our data indicated that the MMP-9 -1562 C/T polymorphism was related with the risk of sepsis (CT vs. CC: P = 0.033, odds ratio (OR) = 1.45, 95% confidence interval (CI) 1.03–2.05; TT+CT vs. CC: P = 0.019, OR = 1.49, 95% CI 1.07–2.07). Stratified analyses demonstrated that this effect was more evident in smokers, drinkers, females and overweight individuals. Furthermore, cross-over analyses suggested that the combined effect of smoking and CT genotype of -1562 C/T polymorphism contributed to the risk of sepsis. In addition, MMP-9 serum levels were significantly lower in sepsis patients than in controls. The MMP-9 -1562 C/T polymorphism was significantly associated with decreased MMP-9 serum levels. Lastly, we observed that this polymorphism was connected to the mortality of sepsis. In conclusion, the interaction between the MMP-9 -1562 C/T polymorphism and smoking correlated with the risk of sepsis in Han Chinese. This polymorphism may serve as a diagnostic marker for sepsis patients.     

Serum γ-glutamyl Transferase Levels,Insulin Resistance and Liver Fibrosis in Patients with Chronic Liver Diseases

Background and Aims

Serum levels of γ-glutamyl-transpeptidase(γ-GT) were associated with liver disease severity and metabolic alterations, which in turn are able to affect hepatic damage. In patients with nonalcoholic fatty liver disease (NAFLD), genotype 1 chronic hepatitis C (G1CHC) and chronic hepatitis B (CHB), we assessed the link between liver fibrosis and γ-GT serum levels, and we evaluated if normal or high γ-GT serum levels affect the association between insulin resistance (IR) and severity of liver fibrosis.

Methods

843 consecutive patients with chronic liver disease (CLD)(193 NAFLD, 481 G1CHC, 169 CHB) were evaluated by liver biopsy (Kleiner and Scheuer scores) and clinical and metabolic measurements. IR was diagnosed if HOMA>3. A serum γ-GT concentration of >36 IU/L in females and >61 IU/L in males was considered the threshold value for identifying high levels of γ-GT.

Results

By multivariate logistic regression analysis, abnormal γ-GT serum levels were independently linked to severe liver fibrosis in patients with NAFLD (OR2.711,CI1.120–6.564,p = 0.02), G1CHC (OR3.461,CI2.138–5.603,p<0.001) and CHB (OR2.778,CI1.042–7.414,p = 0.04), together with IR and liver necroinflammation, and with a negative predictive value>80%. Interestingly, among patients with high or normal γ-GT values, even if IR prevalence was significantly higher in patients with severe fibrosis compared to those without, IR remained significantly associated with severe fibrosis in patients with abnormal γ-GT values only (OR4.150,CI1.079–15.970,p = 0.03 for NAFLD; OR2.250,CI1.211–4.181,p = 0.01 for G1CHC; OR3.096,CI2.050–34.220,p = 0.01 for CHB).

Conclusions

In patients with CLD, IR is independently linked to liver fibrosis only in patients with abnormal γ-GT values, without differences according to liver disease etiology, and suggesting a role of γ-GT as a marker of metabolic-induced liver damage. These data could be useful for the clinical and pharmacologic management of patients with CLD.