Relationships between PON1 Q192R polymorphism and clinical outcome of antiplatelet treatment after percutaneous coronary intervention: a meta-analysis

This meta-analysis was performed to assess the relationships between the PON1 Q192R (rs662 T>C) polymorphism and the clinical outcome of antiplatelet treatment after percutaneous coronary intervention (PCI). A range of electronic databases were searched: Web of Science (1945–2013), the Cochrane Library Database (Issue 12, 2013), PubMed (1966–2013), EMBASE (1980–2013), CINAHL (1982–2013) and the Chinese Biomedical Database (CBM) (1982–2013) without language restrictions. Meta-analysis was conducted using the STATA 12.0 software. The crude odds ratio (OR) with their 95 % confidence interval (CI) were calculated. Six clinical cohort studies with a total number of 5,189 patients undergoing PCI for coronary heart disease were included. Our meta-analysis revealed that the PON1 Q192R polymorphism was correlated with an increased risk of major adverse cardiovascular events (MACE) in patients receiving antiplatelet treatment after PCI (C allele vs. T allele: OR = 1.22, 95 % CI 1.04–1.43, P = 0.014; CT+CC vs. TT: OR = 1.38, 95 % CI 1.03–1.86, P = 0.029; CC vs. TT: OR = 1.45, 95 % CI 1.05–1.99, P = 0.024; respectively), especially among Asians. Furthermore, we found significantly positive correlations between the PON1 Q192R polymorphism and the incidence of stent thrombosis in patients receiving antiplatelet treatment after PCI (C allele vs. T allele: OR = 1.42, 95 % CI 1.08–1.87, P = 0.011; CT+CC vs. TT: OR = 1.93, 95 % CI 1.01–3.67, P = 0.046; CC vs. TT: OR = 2.18, 95 % CI 1.09–4.35, P = 0.027; respectively). Our meta-analysis of clinical cohort studies provides evidence that the PON1 Q192R polymorphism may increase the risk of MACE and stent thrombosis in patients receiving antiplatelet treatment after PCI.     

Genetic polymorphisms in VDR,ESR1 and ESR2 genes may contribute to susceptibility to Parkinson’s disease: a meta-analysis

We conducted this meta-analysis of relevant case–control studies to investigate the relationships between genetic polymorphisms in VDR, ESR1 and ESR2 genes to the susceptibility of Parkinson’s disease (PD). A search on electronic databases without any language restrictions was conducted: MEDLINE (1966–2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980–2013), CINAHL (1982–2013), Web of Science (1945–2013) and the Chinese Biomedical Database (1982–2013). Meta-analysis was performed using the STATA statistical software. Crude odds ratio (OR) with their 95 % confidence interval (95 % CI) was calculated. Fourteen case–control studies with a total of 3,689 PD patients and 4,627 healthy subjects were included in our meta-analysis. The results of our meta-analysis demonstrated that the VDR genetic polymorphisms might be closely related to increased risks of PD (allele model: OR = 1.18, 95 % CI 1.09–1.29, P < 0.001; dominant model: OR = 1.37, 95 % CI 1.16–1.63, P < 0.001; respectively), especially for the polymorphisms rs7976091 and rs10735810. Our findings also illustrated that ESR1 genetic polymorphisms might increase the risk of PD (allele model: OR = 1.56, 95 % CI 1.17–2.07, P = 0.002; recessive model: OR = 1.93, 95 % CI 1.33–2.80, P < 0.001; homozygous model: OR = 1.35, 95 % CI 1.02–1.79, P = 0.038; heterozygous model: OR = 2.04, 95 % CI 1.36–3.07, P = 0.001; respectively), especially for the polymorphisms rs2234693 and rs9340799. Furthermore, we found significant correlations of ESR2 genetic polymorphisms with the risk of PD (allele model: OR = 1.78, 95 % CI 1.19–2.67, P = 0.005; recessive model: OR = 1.93, 95 % CI 1.15–3.27, P = 0.014; homozygous model: OR = 1.77, 95 % CI 1.09–2.89, P = 0.022; heterozygous model: OR = 1.88, 95 % CI 1.08–3.27, P = 0.025; respectively), especially for the rs1256049 polymorphism. Our meta-analysis suggests that genetic polymorphisms in VDR, ESR1 and ESR2 genes may contribute to increased risks for PD.     

Aberrant promoter methylation of RASSF1A gene may be correlated with colorectal carcinogenesis: a meta-analysis

We conducted a meta-analysis of cohort studies to evaluate the potential role of RASSF1A promoter methylation in colorectal carcinogenesis. A range of electronic databases were searched: PubMed (1966–2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980–2013), CINAHL (1982–2013), Web of Science (1945–2013) and the Chinese Biomedical Database (CBM) (1982–2013) without language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude odds ratio (OR) with 95 % confidence interval (95 % CI) was calculated. Eleven clinical cohort studies with a total of 1,505 colorectal cancer (CRC) patients that met all inclusion criteria were included in our meta-analysis. The results of our meta-analysis revealed that the frequency of RASSF1A promoter methylation was strongly correlated with clinical stage (OR = 1.69, 95 % CI 1.16–2.44, P = 0.006), histological grade (OR = 1.92, 95 % CI 1.22–3.04, P = 0.005) and distant metastasis (OR = 2.59, 95 % CI 1.46–4.60, P = 0.037) of CRC patients. However, we observed no positive correlations of RASSF1A promoter methylation with gender (OR = 1.04, 95 % CI 0.74–1.46, P = 0.842), age (OR = 1.70, 95 % CI 0.98–2.93, P = 0.057) and lymph node metastasis (OR = 1.65, 95 % CI 0.87–3.14, P = 0.127) of CRC patients. Further subgroup analysis by ethnicity demonstrated that RASSF1A promoter methylation was correlated with clinicopathological characteristics of CRC patients among Asians (clinical stage: OR = 2.55, 95 % CI 1.55–4.20, P < 0.001; histological grade: OR = 2.70, 95 % CI 1.44–5.06, P = 0.002; lymph node metastasis: OR = 4.09, 95 % CI 1.49–11.26, P = 0.006; distant metastasis: OR = 5.38, 95 % CI 1.73–16.70, P = 0.004), but not among Caucasians and Africans (all P > 0.05). Our meta-analysis has shown positive correlations between aberrant promoter methylation of RASSF1A gene and clinicopathological characteristics of CRC patients, especially among Asians.     

Role of p16 gene promoter methylation in gastric carcinogenesis: a meta-analysis

This meta-analysis was performed to evaluate the relationships between promoter DNA methylation in tumor suppressor gene p16 and gastric carcinogenesis. The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library and CBM databases were searched for relevant articles published before November 1st, 2013 without any language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude odds ratios (ORs) with 95 % confidence intervals (95 % CI) were calculated. Forty-seven clinical cohort studies that met all inclusion criteria were included in this meta-analysis. A total of 2,813 gastric cancer (GC) patients were assessed. Our meta-analysis results revealed that the frequencies of p16 promoter methylation in the GC tissues were higher than those of normal and adjacent tissues (Normal: OR = 23.04, 95 % CI = 13.55–39.15, P < 0.001; Adjacent: OR = 4.42, 95 % CI = 1.66–11.76, P = 0.003; respectively). Furthermore, we observed significant associations of p16 promoter methylation with TNM stage, histologic grade, invasive grade, lymph node metastasis of GC (TNM stage: OR = 3.60, 95 % CI: 2.17–5.98, P < 0.001; Histologic grade: OR = 2.63, 95 % CI: 1.55–4.45, P < 0.001; Invasive grade: OR = 3.44, 95 % CI: 1.68–7.06, P = 0.001; Lymph node metastasis: OR = 2.68, 95 % CI: 1.66–4.32, P < 0.001; respectively). However, there were no correlations of p16 promoter methylation with the TNM stage and Helicobacter pylori (HP) infection of GC (Tumor size: OR = 0.76, 95 % CI: 0.14–4.07, P = 0.746; HP infection: OR = 1.31, 95 % CI: 0.75–2.27, P = 0.342; respectively). Our findings provide empirical evidence that p16 promoter methylation may play an important role in gastric carcinogenesis. Thus, p16 promoter methylation may be a promising potential biomarker for the early diagnosis of GC.     

Toll-like receptor (TLR) and matrix metalloproteinase (MMP) polymorphisms and periodontitis susceptibility: a meta-analysis

The aim of this study was to determine whether the toll-like receptor (TLR) and matrix metalloproteinase (MMP) polymorphisms confers susceptibility to periodontitis in ethnically different populations. A literature search using PubMed and Embase provided the data to conduct a meta-analysis on the associations between the TLR2 Arg753Gln, TLR4 Asp299Gly, Thr399Ile, MMP-1 ?1607 G1/G2 and MMP-9 ?1562 C/T polymorphisms and periodontitis. A total of 32 studies (14 on TLR polymorphisms and 18 on MMP polymorphisms) were considered in the meta-analysis. The meta-analysis showed no association between periodontitis and the TLR2 753Arg allele (Odds ratio [OR] = 0.962, 95 % confidence interval [CI] = 0.662–1.400, p = 0.841). Meta-analysis of the TLR4 Asp299Gly and Thr399Ile polymorphisms showed no association between periodontitis and the TLR4 299Asp allele in all study subjects (OR = 0.984, 95 % CI = 0.761–1.271, p = 0.900; OR = 1.030, 95 % CI = 0.748–1.418, p = 0.854). Meta-analysis showed an association between the MMP-1 ?1607 G2G2 genotype and periodontitis in Asians (OR = 3.778, 95 % CI = 1.210–11.80, p = 0.022). Meta-analysis containing only studies in Hardy–Weinberg equilibrium revealed no association between chronic periodontitis and the MMP-9 ?1562TT genotype (OR = 0.638, 95 % CI = 0.265–1.533, p = 0.315). This meta-analysis demonstrates a lack of association between the TLR2 Arg753Gln, TLR4 Asp299Gly, Thr399Ile, MMP-9 ?1562 C/T polymorphisms and periodontitis, but shows an association between the MMP-1 ?1607 G2G2 genotype and periodontitis in Asians.     

Tumor Necrosis Factor Alpha and Interleukin 10 Promoter Polymorphisms in Mexican Patients with Restenosis After Coronary Stenting

To test for an association with risk for restenosis after coronary stent placement, the TNF-α and IL-10 polymorphisms were analyzed by 5′ exonuclease TaqMan assays in 162 patients who initially underwent coronary stenting. Analysis of basal and procedure coronary angiographies revealed a higher proportion of restenosis in lesions treated with bare metal stents compared with those treated with drug-eluting stents (P < 0.001). Distribution of TNF-α genotypes was similar in patients with and without restenosis. The IL-10 polymorphisms showed a moderate protective trend of the ?819 TT genotype against restenosis when the lesions were analyzed (P = 0.071, OR = 0.471). Multivariate analysis confirmed a protective role for drug-eluting stents (P < 0.001, OR = 0.199) and the ?819 TT genotype (P = 0.037, OR = 0.391). These results suggest the IL-10 ?819 TT genotype has a protective role against in-stent restenosis.     

Apo A5 −1131T/C, FgB −455G/A, −148C/T, and CETP TaqIB gene polymorphisms and coronary artery disease in the Chinese population: a meta-analysis of 15,055 subjects

The Apolipoprotein A5 (APO A5) ?1131T/C, fibrinogen β (FgB) ?455G/A, ?148C/T, and cholesteryl ester transfer protein (CETP) TaqIB gene polymorphisms have been indicated to be associated with the coronary artery disease (CAD) risk, but the individual study results are still inconsistent. To explore the relationship between APO A5 ?1131T/C, FgB ?455G/A, ?148C/T, and CETP TaqIB gene polymorphisms and CAD in the Chinese population, the current meta-analysis involving 15,055 subjects from 40 individual studies was conducted. The pooled odds ratio (OR) for the association between APO A5 ?1131T/C, FgB ?455G/A, ?148C/T, and CETP TaqIB gene polymorphisms and CAD and its corresponding 95 % confidence interval (95 % CI) were evaluated by random or fixed effect model. A significant association between APO A5 ?1131T/C gene polymorphism and CAD in the Chinese population was found under an allelic (OR: 1.33, 95 % CI: 1.22–1.44, P < 0.00001), recessive (OR: 1.67, 95 % CI: 1.25–2.25, P = 0.0006), dominant (OR: 0.820, 95 % CI: 0.767–0.876, P = 1.0 × 10^?10), homozygous (OR: 2.36, 95 % CI: 1.55–3.58, P < 0.0001) and heterozygous genetic models (OR: 1.136, 95 % CI:1.075–1.200, P = 1.0 × 10^?10). A significant association between FgB ?455G/A gene polymorphism and CAD was also detected in the Chinese population under an allelic (OR: 1.50, 95 % CI: 1.25–1.81, P < 0.0001), dominant (OR: 0.864, 95 % CI: 0.819–0.912, P = 1.0 × 10^?10), homozygous (OR: 1.616, 95 % CI: 1.213–2.152, P = 0.001) and heterozygous genetic models (OR: 1.245, 95 % CI:1.138–1.361, P = 1.0 × 10^?10). No significant association was found between them under a recessive genetic model (OR: 1.124, 95 % CI: 0.844–1.497, P = 0.424). A significant association was also found between FgB ?148C/T gene polymorphism and CAD in the Chinese population under an allelic (OR: 1.34, 95 % CI: 1.06–1.71, P = 0.02), recessive (OR: 1. 65, 95 % CI: 1.02–2.69, P = 0.04), dominant (OR: 0.924, 95 % CI: 0.872–0.978, P = 0.007) and homozygous genetic models (OR: 0.968, 95 % CI: 0.942–0.995, P = 0.018). No significant association was found between them under a heterozygous genetic model (OR: 0.979, 95 % CI: 0.937–1.023, P = 0.342). In the whole Chinese population, no significant association between the CETP TaqIB gene polymorphism and CAD was found under an allelic (OR: 1.17, 95 % CI: 0.94–1.45, P = 0.15), dominant (OR: 1.46, 95 % CI: 0.80–2.67, P = 0.22) or recessive genetic models (OR: 0.68, 95 % CI: 0.32–1.44, P = 0.31). However, in the subgroup analysis stratified by ethnicity, there was a significant association between them under an allelic (OR: 1.27, 95 % CI: 1.07–1.52, P = 0.007) and dominant genetic model (OR: 2.04, 95 % CI: 1.49–2.79, P < 0.00001) in the Han subgroup. In the Chinese population, the APO A5 ?1131T/C and FgB ?455G/A, ?148C/T gene polymorphisms were implied to be associated with CAD susceptibility. The APO A5 ?1131C, FgB ?455A, and ?148T alleles might confer susceptibility to CAD. CETP TaqIB gene polymorphism was suggested to be associated with CAD susceptibility in the Chinese Han population. Carriers with B1 allele of CETP TaqIB gene might be predisposed to CAD in the Chinese Han population.     

Non-alcoholic fatty liver disease and risk of in-stent restenosis after bare metal stenting in native coronary arteries

In-stent restenosis (ISR) remains the most common complication of percutaneous coronary intervention. Due to shared risk factors, it is postulated that non-alcoholic fatty liver disease (NAFLD) patients have an increased risk of ISR. This study aimed to determine the association between NAFLD and ISR in patients after bare metal stenting. This study included a cohort of 210 consecutive patients (150 men and 60 women) undergoing follow-up angiography. The primary end-point was angiographic ISR. Multivariate logistic regression analysis was used to identify independent risk factors for ISR. The cumulative ISR rate during follow-up was analyzed by Kaplan–Meier method. Subgroup analyses were also done for different gender. The ISR rate was 29.5 %. Patients with NAFLD had a significantly higher prevalence of ISR than patients without NAFLD (43.3 vs. 16.0 %, P < 0.001). In logistic regression analysis, NAFLD was associated with increased ISR, independent of low-density lipoprotein cholesterol, body mass index (adjusted odds ratio: 2.688, 95 % confidence intervals: 1.285–5.537, P < 0.001). Male NAFLD patients had a higher prevalence of ISR than patients without NAFLD (48.4 vs. 15.3 %, P < 0.001), while the prevalence of ISR in female patients with and without NAFLD were comparable (7.7 vs. 17.0 %, P = 0.404). Kaplan–Meier analysis showed a significant association between NAFLD and ISR in all patients (log-rank P = 0.008) and in male subgroup (log-rank P = 0.033), but not in female subgroup (log-rank P = 0.313). This preliminary study suggests that NAFLD could independently associate with a high prevalence of ISR, especially in male patients.     

Meta-analysis demonstrates lack of association of the GSK3B −50C/T polymorphism with risk of bipolar disorder

Published data on the association between GSK3B ?50C/T (rs334558) and bipolar disorder (BD) are inconclusive. We performed this meta-analysis to evaluate the relationship of this single-nucleotide polymorphism with the susceptibility, and with the age at onset of BD. A literature search was conducted though PubMed, EMBASE, Web of Science and China National Knowledge Infrastructure databases to identify relevant studies up to February 14, 2014. We identified a total of 6 publications including 1,251 cases and 1,804 controls to investigate the effect of GSK3B ?50C/T on BD risk, and found no significant association in any genetic models (C vs. T: OR = 1.03, 95 % CI: 0.92–1.15; CC vs. TT+TC: OR = 1.04, 95 % CI: 0.84–1.28; TC+CC vs. TT: OR = 1.16, 95 % CI: 0.97–1.39; and CC vs. TC vs. TT: OR = 1.08, 95 % CI: 0.96–1.22). Subgroup analysis by ethnicity did not change the results. The association between GSK3B ?50C/T and age at onset of BD was explored by 6 identified studies with a total of 659 BD type I patients. Similarly, we did not observe significant results in any genetic models (TC+CC vs. TT: SMD = 0.20, 95 % CI: ?0.07 to 0.47; CC vs. TT+TC: SMD = 0.11, 95 % CI: ?0.10 to 0.32; CC vs. TT: SMD = 0.32, 95 % CI: ?0.13 to 0.77). The power analysis and tests for publication bias ensured the reliability of our results. In summary, this meta-analysis suggests that the functional polymorphism ?50C/T within the GSK3B gene promoter is unlikely to relate with BD risk. However, more larger and well-designed studies are still needed to yield a conclusive result on the topic.     

Prognostic factors in infective endocarditis in general hospitals in the Netherlands

Introduction

Despite advances in treatment, infective endocarditis (IE) still ranks amongst the most lethal infectious diseases. We sought to determine prognostic factors in general hospitals in the Netherlands as research in this setting is scarce.

Results

Between 2004 and 2011, we identified 216 cases of IE, 30.1?% of which were prosthetic valve IE. This leads to an annual incidence of IE of 5.7 new cases per 100,000 persons per year. Women were less likely to undergo surgical intervention (OR = 1.96, 95?% CI 1.06–3.61, p = 0.031). Also, ageing was an independent prognostic factor for not receiving surgery in a multivariate analysis (annual OR = 1.04, 95?% CI 1.02–1.06, p < 0.001). Female sex was a prognostic factor for mortality (OR = 2.35, 95?% CI 1.29–4.28, p = 0.005). Age was also an independent prognostic factor for mortality (OR = 1.05, 95% CI 1.03–1.08, p < 0.001). Conservative treatment was a prognostic factor for mortality (OR = 3.39, 95?% CI 1.80–6.38, p < 0.001) whereas surgical intervention was an independent prognostic factor for adverse events (OR = 3.03, 95% CI 1.64–5.55, p < 0.001). Staphylococcus aureus was an independent prognostic factor for adverse events (OR = 2.05, 95?% CI 1.10–3.84, p = 0.024) but not for mortality.

Conclusion

This study shows that endocarditis in general hospitals has a high rate of morbidity and mortality. Even when treated, it ranks as one of the most lethal infectious diseases in the Netherlands, especially in women and the elderly.

     

Quantitative analysis of the association between interleukin-10 1082A/G polymorphism and susceptibility to sepsis

There are some epidemiological studies investigating the association between interleukin-10 (IL-10) 1082A/G polymorphism and sepsis susceptibility reporting conflicting findings. Our work tried to further quantitatively assess the association of the IL-10 1082A/G polymorphism with sepsis susceptibility through a systematic review and meta-analysis. A total of eleven studies with 2,528 subjects were finally included into the meta-analysis. Pooled odds ratios (ORs) and corresponding 95 % confidence intervals (95 % CIs) were calculated with random-effects model or fixed-effects model based on the heterogeneity among the included studies. Meta-analysis of all 11 studies showed that there was an obvious association between IL-10 1082A/G polymorphism and sepsis susceptibility under the allele comparison model (G vs A) and the codominant model (GG vs AA) (for G vs A: OR = 0.83, 95 % CI 0.72–0.96, P = 0.011; for GG vs AA: OR = 0.67, 95 % CI 0.47–0.96, P = 0.029). Subgroup analysis by ethnicity showed that there was an obvious association between IL-10-1082A/G polymorphism and sepsis susceptibility in Asians under three comparison models (for G vs A: OR = 0.75, 95 % CI 0.62–0.91, P = 0.004; for GG vs AA: OR = 0.39, 95 % CI 0.21–0.73, P = 0.003; for GG vs AA/AG: OR = 0.36, 95 % CI 0.14–0.92, P = 0.032), but there was no similar association in Caucasians under all four comparison models. Our meta-analysis reveals that the IL-10-1082A/G polymorphism has an association with the susceptibility to sepsis in Asian populations. Further studies are needed to investigate the effect of IL-10-1082A/G polymorphism on sepsis susceptibility in Caucasians.     

Significant association of glutathione S-transferase T1 null genotype with esophageal cancer risk: a meta-analysis

Recent studies on the association between glutathione S-transferase T1 (GSTT1) polymorphism and risk of esophageal cancer showed inconclusive results. To clarify this possible association, we conducted a meta-analysis of published studies. Data were collected from the following electronic databases: Pubmed, Embase, and Chinese Biomedical Database (CBM). The odds ratio (OR) and its 95 % confidence interval (95 % CI) was used to assess the strength of this association. We summarized the data on the association between GSTT1 null genotype and risk of esophageal cancer in the overall population, and performed subgroup analyses by ethnicity. Finally, a total of 24 independent studies including a total of 7,801 subjects (2,965 cases and 4,836 controls) were eligible for meta-analysis. In the overall analysis, there was no significant association between GSTT1 null genotype and esophageal cancer risk (OR = 1.15, 95 % CI 0.99–1.33, P = 0.067). However, meta-analysis of adjusted ORs showed a significant association between GSTT1 null genotype and increased risk of esophageal cancer (OR = 1.30, 95 % CI 1.08–1.56, P = 0.005). Subgroup analyses by ethnicity showed there was an obvious association between GSTT1 null genotype and increased risk of esophageal cancer in East Asians (OR = 1.24, 95 % CI 1.10–1.39, P < 0.001), but not in Caucasians (OR = 0.89, 95 % CI 0.71–1.11, P = 0.300). There was no obvious risk of publication bias in this meta-analysis (Egger’s test, P = 0.784). This meta-analysis demonstrates that GSTT1 null genotype is independently associated with increased risk of esophageal cancer, and a race-specific effect may exist in this association.     

Toll-like receptor polymorphisms and vasculitis susceptibility: meta-analysis and systematic review

The aim of this study was to determine whether toll-like receptor (TLR) polymorphisms confers susceptibility to vasculitis. A literature search was conducted using the PubMed and Embase. A meta-analysis on the associations between the TLR4 Asp299Gly polymorphisms and vasculitis was carried out using allele contrast, dominant, and codominant models and a systematic review of other TLR polymorphisms. Fourteen studies involving 2,064 patients and 2,481 controls were included in this systematic review, which comprised nine on Behcet’s disease (BD), three on giant cell arteritis (GCA), and one on Henoch–Schenlein purpura (HSP). Meta-analysis of six studies showed a significant association between the Gly/Gly+Gly/Asp genotype of the TLR4 Asp299Gly polymorphism and vasculitis and GCA (Odds ratio [OR] = 1.368, 95 % confidence interval [CI] = 1.300–1.815, p = 0.030; OR = 1.523, 95 % CI = 1.099–2.112, p = 0.012). Under a random effects model, the adjusted ORs calculated using the trim and fill technique revealed an association between the Gly/Gly+Gly/Asp genotype of the TLR4 Asp299Gly polymorphism and vasculitis (OR = 1.544, 95 % CI = 1.091–2.185, p < 0.05). Stratification by vasculitis type using the codominant model showed the trend for the association with GCA (OR = 1.569, 95 % CI = 0.970–2.538, p = 0.066). There were three studies on the TLR2 Arg753Gln polymorphism and two on the TLR4 Thr399Ile polymorphism; no association with vasculitis was evident. Among the TLR2, TLR7, and TLR9 polymorphisms included in this review, one Asian study revealed a significant association between the TLR7 rs5743733 and rs3853839 with BD (p = 0.002, 0.036) and one Asian study showed an association of TLR9 rs352140 with BD (p = 0.009). This meta-analysis demonstrates that the TLR4 Asp299Gly polymorphism may confer susceptibility to GCA. The review of published data suggests that other TLR polymorphisms such as TLR7 and TLR9 may play a role in vasculitis.     

Excimer laser coronary angioplasty and intracoronary radiation for in-stent restenosis: Six-month angiographic and clinical outcomes

Background: The purpose of this study was to evaluate 6-month clinical and angiographic outcomes in patients treated with excimer laser coronary angioplasty (ELCA) and intracoronary radiation (ICR) for in-stent restenosis (ISR).Methods: A consecutive series of 175 patients with ISR treated with ELCA+ICR (gamma and beta emitters) were compared to 33 patients with ISR treated with ELCA alone. Baseline characteristics were similar between groups. ELCA+ICR and ELCA-alone patients had similar lesion lengths (25.0±12.0 vs. 24.0±16.8 mm, P=NS) in predominantly saphenous vein grafts (SVG, 38% vs. 42%, P=NS).Results: Procedural success was high (ELCA+ICR, 97.0% vs. ELCA alone, 98.5%, P=NS), with no perforations or acute vessel closures. ELCA+ICR therapy reduced target vessel revascularization (TVR; 27% vs. 64%, P<.0001) and major adverse cardiac events [MACE: death, myocardial infarction (MI), or TVR; 30% vs. 64%, P<.0001] compared to ELCA alone. Late loss was 0.66±0.90 mm in ELCA+ICR patients and 0.85±0.60 mm in ELCA-alone patients (P=NS). Angiographic binary restenosis (>50%) was significantly reduced with adjunctive ICR (28% vs. 54%, P=.014).Conclusion: Radiation therapy with ELCA significantly reduces angiographic binary restenosis at 6 months in patients with diffuse ISR, driven predominantly by reduced percutaneous TVR.     

Significant association between GSTT1 null genotype and risk of asthma during childhood in Caucasians

Asthma is a complex multifactorial disorder and its management requires a better understanding of its various pathogenesis and mechanisms. Previous studies assessing the association between glutathione S-transferase T1 (GSTT1) null genotype and asthma risk during childhood reported conflicting results. To get a more precise estimation of the association between GSTT1 null genotype and risk of asthma during childhood, we performed a meta-analysis of 16 studies with a total of 18,558 subjects. Subgroup analyses were performed by ethnicity. The pooled odds ratio (OR) with corresponding 95 % confidence interval (95 %CI) was used to assess the association. Overall, there was a significant association between GSTT1 null genotype and increased risk of children asthma (OR = 1.25, 95 % CI, 1.02–1.54; P = 0.032). Subgroup analyses showed GSTT1 null genotype was associated with increased risk of children asthma in Caucasians (OR = 1.46, 95 % CI, 1.04–2.03; P = 0.027), but not in Asians (OR = 1.03, 95 % CI, 0.55–1.94; P = 0.928) and Africans (OR = 1.33, 95 % CI, 0.92–1.91; P = 0.127). There was no evidence of publication bias in the subgroup analysis of Caucasians. In conclusion, there is a significant association between GSTT1 null genotype and risk of asthma during childhood in Caucasians. More well-designed epidemiological studies are needed to further assess this association in Asians and Africans.     

Variants in toll-like receptors 2 and 9 influence susceptibility to pulmonary tuberculosis in Caucasians, African-Americans, and West Africans

Tuberculosis (TB) is a global public health problem and a source of preventable deaths each year, with 8.8 million new cases of TB and 1.6 million deaths worldwide in 2005. Approximately, 10% of infected individuals develop pulmonary or extrapulmonary TB, suggesting that host defense factors influence development of active disease. Toll-like receptor’ (TLR) polymorphisms have been associated with regulation of TLR expression and development of active TB. In the present study, 71 polymorphisms in TLR1, TLR2, TLR4, TLR6, and TLR9 were examined from 474 (295 cases and 179 controls) African-Americans, 381 (237 cases and 144 controls) Caucasians, and from 667 (321 cases and 346 controls) Africans from Guinea-Bissau for association with pulmonary TB using generalized estimating equations and logistic regression. Statistically significant associations were observed across populations at TLR9 and TLR2. The strongest evidence for association came at an insertion (I)/deletion (D) polymorphism (?196 to ?174) in TLR2 that associated with TB in both Caucasians (II vs. ID&DD, OR = 0.41 [95% CI 0.24–0.68], p = 0.0007) and Africans (II vs. ID&DD, OR = 0.70 [95% CI 0.51–0.95], p = 0.023). Our findings in three independent population samples indicate that variations in TLR2 and TLR9 might play important roles in determining susceptibility to TB.     

Association of CDKN1B gene polymorphisms with susceptibility to breast cancer: a meta-analysis

A number of case–control studies have been conducted to investigate the association of CDKN1B gene polymorphisms with breast cancer. However, these studies reported conflicting results. The aim of our study was to quantitatively summarize the association of CDKN1B gene polymorphisms with breast cancer. Systemic searches of the PubMed, Excerpta Medica Database, and Chinese Biomedical Literature Database databases were performed, with the last report up to Oct 2012. Odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of the association. Seven studies including 6,822 cases and 7,186 controls were involved in this meta-analysis, which was performed for two CDKN1B gene polymorphisms (rs2066827 and rs34330). Significant association was found for rs34330 polymorphism (T versus C: OR = 1.10, 95 % CI = 1.03–1.18, P = 0.003; CT + TT versus CC: OR = 1.38, 95 % CI = 0.98–1.93, P = 0.07; TT versus CC + CT: OR = 1.06, 95 % CI = 0.93–1.21, P = 0.38; TT versus CC: OR = 1.23, 95 % CI = 1.04–1.45, P = 0.02; CT versus CC: OR = 1.42, 95 % CI = 0.97–2.09, P = 0.07), but not for rs2066827 polymorphism (G versus T: OR = 0.99, 95 % CI = 0.91–1.08, P = 0.84; TG + GG versus TT: OR = 0.98, 95 % CI = 0.89–1.08, P = 0.69; GG versus TT + TG: OR = 1.04, 95 % CI = 0.83–1.30, P = 0.75; GG versus TT: OR = 1.03, 95 % CI = 0.82–1.30, P = 0.77; TG versus TT: OR = 0.97, 95 % CI = 0.88–1.08, P = 0.58). This meta-analysis suggests that breast cancer may be associated with CDKN1B gene rs34330 polymorphism, but not rs2066827 polymorphism.     

The association between CD14 gene C-260T polymorphism and coronary heart disease risk: a meta-analysis

Monocyte differentiation antigen CD14 is considered an important cell-activating mediator of inflammatory responses that may result in atherosclerosis, coronary heart disease (CHD), thrombus formation, and myocardial infarction (MI). A common C-260T polymorphism in the promoter of the CD14 gene, the trans-membrane receptor of lipopolysaccharides, has been inconsistently associated with CHD. To investigate this inconsistency, we performed a meta-analysis of 28 studies involving a total of 13,335 CHD cases and 7,979 controls for C-260T of the CD14 gene to evaluate the effect of CD14 on genetic susceptibility for CHD. An overall random effects odds ratio of 1.24 (95 % CI: 1.12–1.36, P < 10^?5) was found for T allele. Significant results were also observed using dominant (OR = 1.34, 95 % CI: 1.17–1.54, P < 10^?4) or recessive genetic model (OR = 1.25, 95 % CI: 1.10–1.41, P = 0.0004). There was strong evidence of heterogeneity (P < 10^?5), which largely disappeared after stratification by ethnicity. After stratified by ethnicity, significant results were found in East Asians; whereas no significant associations were found among Caucasians and other ethnic populations in all genetic models. In the stratified analysis according to sample size, CHD endpoints, and HWE status, significantly increased risks for the polymorphism were found in all genetic models. In conclusion, our results indicate that the CD14 C-260T polymorphism is a risk factor of CHD, especially in East Asians. However, additional very large-scale studies are warranted to confirm our results.     

Genetic variants in microRNA and microRNA biogenesis pathway genes and breast cancer risk among women of African ancestry

MicroRNAs (miRNA) regulate breast biology by binding to specific RNA sequences, leading to RNA degradation and inhibition of translation of their target genes. While germline genetic variations may disrupt some of these interactions between miRNAs and their targets, studies assessing the relationship between genetic variations in the miRNA network and breast cancer risk are still limited, particularly among women of African ancestry. We systematically put together a list of 822 and 10,468 genetic variants among primary miRNA sequences and 38 genes in the miRNA biogenesis pathway, respectively; and examined their association with breast cancer risk in the ROOT consortium which includes women of African ancestry. Findings were replicated in an independent consortium. Logistic regression was used to estimate the odds ratio (OR) and 95 % confidence intervals (CI). For overall breast cancer risk, three single-nucleotide polymorphisms (SNPs) in miRNA biogenesis genes DROSHA rs78393591 (OR = 0.69, 95 % CI: 0.55–0.88, P = 0.003), ESR1 rs523736 (OR = 0.88, 95 % CI: 0.82–0.95, P = 3.99 × 10^?4), and ZCCHC11 rs114101502 (OR = 1.33, 95 % CI: 1.11–1.59, P = 0.002), and one SNP in primary miRNA sequence (rs116159732 in miR-6826, OR = 0.74, 95 % CI: 0.63–0.89, P = 0.001) were found to have significant associations in both discovery and validation phases. In a subgroup analysis, two SNPs were associated with risk of estrogen receptor (ER)-negative breast cancer, and three SNPs were associated with risk of ER-positive breast cancer. Several variants in miRNA and miRNA biogenesis pathway genes were associated with breast cancer risk. Risk associations varied by ER status, suggesting potential new mechanisms in etiology.     

The l58Val/Met polymorphism of catechol-O-methyl transferase gene and prostate cancer risk: a meta-analysis

The association between COMT Val158Met polymorphism and prostate cancer has been evaluated. However, the results of these studies on the association remain conflicting. To derive a more precise estimation of the relationship, a meta-analysis was performed. A comprehensive search was conducted to identify the eligible studies of COMT Val158Met polymorphism and prostate cancer risk. Summary odds ratios (OR) and 95 % confidence interval (CI) for COMT Val158Met polymorphism and prostate cancer were calculated. Statistical analysis was performed with the software program Review Manage (Version 5.0) and Stata (Version 12.0). Six case–control studies, totally 4,118 persons including 2,143 cases and 1,975 controls, met the included criteria and thus were selected. Our analysis suggested that Val158Met polymorphism was associated with prostate cancer risk in overall population. Collectively, the results of the present study suggest that significant associations of COMT Val158Met polymorphisms with prostate cancer were observed (for additive model: OR = 1.068, 95 % CI = 1.002–1.138, P _{heterogeneity} = 0.363, P = 0.043; for dominant model: OR = 1.266, 95 % CI = 1.057–1.517, P _{heterogeneity} = 0.000, P = 0.011; for recessive model: OR = 1.050, 95 % CI = 0.961–1.146, P _{heterogeneity} = 0.558, P = 0.279; and Val allele versus Met allele OR = 0.932, 95 % CI = 0.894–0.971, P _{heterogeneity} = 0.272, P = 0.001). In the subgroup analysis, we detected no significant association between the COMT 158 Val/Met genotype and prostate cancer risk in Caucasian and Asian populations, while the contrary result for additive model (OR = 2.43, 95 % CI = 1.08–5.43, P _{heterogeneity} = 0.04, P = 0.03) in Asian populations. The result of this meta-analysis suggests that COMT l58Val/Met polymorphism might be contributed to the overall prostate cancer risk.