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Asian Pacific Journal of Cancer... 2014A number of studies have identified a shared susceptibility locus in phospholipase C epsilon 1 (PLCE1) for esophageal squamous cell carcinoma (ESCC) and gastric cardia... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A number of studies have identified a shared susceptibility locus in phospholipase C epsilon 1 (PLCE1) for esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinomas (GCA). However, the results of PLCE1 expression in esophageal and gastric cancer remain inconsistent and controversial. Moreover, the effects on clinicopathological features remain undetermined. This study aimed to provide a precise quantification of the association between PLCE1 expression and the risk of ESCC and GCA through meta-analysis.
MATERIALS AND METHODS
Eligible studies were identified from PubMed, Wanfang Data, ISI Web of Science, and the Chinese National Knowledge Infrastructure databases. Using RevMan5.2 software, pooled odds ratios (ORs) with 95% confidence intervals (CIs) were employed to assess the association of PLCE1 expression with clinicopathological features relative to ESCC or GCA.
RESULTS
Seven articles were identified, including 761 esophageal and gastric cancer cases and 457 controls. Overall, we determined that PLCE1 expression was associated with tumor progression in both esophageal cancers (pooled OR=5.93; 95%CI=3.86 to 9.11) and gastric cancers (pooled OR=9.73; 95%CI=6.46 to 14.7). Moreover, invasion depth (pooled OR=3.62; 95%CI=2.30 to 5.70) and lymph node metastasis (pooled OR=4.21; 95%CI=2.69 to 6.59) were linked with PLCE1 expression in gastric cancer. However, no significant associations were determined between PLCE1 overexpression and the histologic grade, invasion depth, and lymph node metastasis in esophageal cancer.
CONCLUSIONS
Our meta- analysis results indicated that upregulated PLCE1 is significantly associated with an increased risk of tumor progression in ESCC and GCA. Therefore, PLCE1 expression can be appropriately regarded as a promising biomarker for ESCC and GCA patients.
Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cardia; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Genetic Predisposition to Disease; Humans; Lymphatic Metastasis; Middle Aged; Phosphoinositide Phospholipase C; Stomach Neoplasms; Upper Gastrointestinal Tract
PubMed: 25520085
DOI: 10.7314/apjcp.2014.15.22.9661 -
Alimentary Pharmacology & Therapeutics Sep 2014Several studies have reported an association between alcoholic liver cirrhosis (ALC) or other forms of alcoholic liver disease (ALD) and the genetic variant rs738409... (Meta-Analysis)
Meta-Analysis Review
Systematic review with meta-analysis: the I148M variant of patatin-like phospholipase domain-containing 3 gene (PNPLA3) is significantly associated with alcoholic liver cirrhosis.
BACKGROUND
Several studies have reported an association between alcoholic liver cirrhosis (ALC) or other forms of alcoholic liver disease (ALD) and the genetic variant rs738409 (C>G) in adiponutrin/patatin-like phospholipase domain-containing 3 gene (PNPLA3).
AIM
To evaluate the influence of this variant on ALC and other forms of ALD.
METHODS
We performed a systematic review of previous studies on the relationship between rs738409 of PNPLA3 and ALD and meta-analysis was conducted in a random-effects model. Calculations of the odds ratios (ORs) and their confidence intervals (CIs), tests for heterogeneity and sensitivity analyses were performed.
RESULTS
Database search identified 11 previous studies available for inclusion with a total of 3495 patients with ALD (2087 with ALC) and 5038 controls (4007 healthy subjects and 1031 alcoholics without ALD). Patients with ALC compared to controls had a significantly higher prevalence of the G allele when comparing GG vs. CC (OR 4.30, 95% CI 3.25-5.69; P < 0.00001) or GC vs. CC genotypes (GC vs. CC: OR 1.91, 95% CI 1.67-2.17) or under a recessive or dominant model. Similar results were found when comparing separately patients with ALC vs. alcoholics without ALD or healthy subjects. An association of the G allele with ALD emerged when comparing ALD patients vs. alcoholics without ALD and/or healthy subjects although moderate to large heterogeneity was observed. Our data suggested an additive genetic model for this variant in ALD.
CONCLUSION
Our meta-analysis shows that the rs738409 variant of PNPLA3 is clearly associated with alcoholic liver cirrhosis.
Topics: Genetic Variation; Humans; Lipase; Liver Diseases, Alcoholic; Membrane Proteins; Odds Ratio
PubMed: 25060292
DOI: 10.1111/apt.12890 -
Journal of Nephrology Apr 2014Detection of M-type phospholipase A2 receptor (PLA2R) can be used in serologic diagnosis of idiopathic membranous nephropathy (IMN), but there are limited data about the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Detection of M-type phospholipase A2 receptor (PLA2R) can be used in serologic diagnosis of idiopathic membranous nephropathy (IMN), but there are limited data about the sensitivity and specificity of its diagnostic values.
METHODS AND RESULTS
Meta-analysis of diagnostic test studies assessing the values of PLA2R in diagnosis of IMN. MEDLINE, EMBASE, and CENTRAL databases and congress abstracts were searched for studies reporting the value of PLA2R to predict IMN. The quality of the studies was evaluated using the guidelines of the updated Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The results are summarized as sensitivity, specificity, and diagnostic odds ratio (OR). Data from 10 studies involving 1,550 participants were analyzed. Across all settings, the diagnostic OR for serum anti-PLA2R level to predict IMN at different stages was 247.41, with sensitivity of 0.69 and specificity of 0.99. The estimated sensitivity and specificity of serum anti-PLA2R level for diagnosis of IMN in the active stage were 74.0 and 95.0%, respectively, with diagnostic OR of 54.22. The estimated sensitivity and specificity of biopsy anti-PLA2R for diagnosis of IMN at different stages was 73.0 and 83.0%, respectively, with diagnostic OR of 13.75.
CONCLUSIONS
This meta-analysis shows that serum anti-PLA2R level is of diagnostic value for IMN in the active stage. Future large-cohort prospective studies are required to reveal the diagnostic value of circulating anti-PLA2R antibodies versus PLA2R antigens in kidney biopsy for IMN at different stages.
Topics: Antibodies; Biopsy; Glomerulonephritis, Membranous; Humans; Kidney; Receptors, Phospholipase A2; Sensitivity and Specificity
PubMed: 24500886
DOI: 10.1007/s40620-014-0042-7 -
Current Cardiology Reviews Nov 2013Studies indicate that elevated plasma concentrations of lipoprotein-associated phospholipase A2 (Lp-PLA2) is associated with increased risk of cardiovascular disease.... (Review)
Review
Studies indicate that elevated plasma concentrations of lipoprotein-associated phospholipase A2 (Lp-PLA2) is associated with increased risk of cardiovascular disease. Lp-PLA2 seems to play a crucial role in the formation of plaques and acute inflammation, and plasma Lp-PLA2 could therefore potentially be used as a predictor of long-term outcome in ACS patients. To evaluate this, data concerning Lp-PLA2 as a predictor in ACS patients was gathered through a systematic literature review, and studies on this issue were extracted from relevant databases, incl. PubMed and Cochrane. A total of 14 articles were retrieved, but after thorough evaluation and elimination of irrelevant articles only seven studies were eligible for the literature review. All studies except two showed significant correlation between Lp-PLA2 and CV events in ACS patients. Only one study found an independent value to predict CV events 30 days after ACS. Altogether, there was inconsistency in the findings regarding the potential use of Lp-PLA2 and a lack of knowledge on several issues. Lp-PLA2 seems to give valuable information on which ACS patients are prone to new events and also provides important information on plaque size. However, more focused studies concerning genetic variations, time-window impact, patients with and without CV risk factors (e.g. diabetes), and treatment effects are needed. In conclusion, Lp-PLA2 offers new insight in the pathophysiological development of ACS, but until the aforementioned issues are addressed the biomarker will mainly be of interest in a research setting, not as a predictive parameter in a clinical setting.
Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Acute Coronary Syndrome; Biomarkers; Cardiovascular Diseases; Humans; Prognosis; Risk Factors
PubMed: 24313641
DOI: 10.2174/1573403x09666131202143349 -
Atherosclerosis Nov 2012Lipoprotein association phospholipase A2 (Lp-PLA(2)), an enzyme which has been found in atherosclerotic plaque is currently under investigation in large Phase III... (Review)
Review
BACKGROUND
Lipoprotein association phospholipase A2 (Lp-PLA(2)), an enzyme which has been found in atherosclerotic plaque is currently under investigation in large Phase III clinical trials of vascular disease prevention. We assessed in a variety of different population settings variation of Lp-PLA(2) mass and activity across gender, ethnicity, diabetes, kidney disease and metabolic syndrome. We also assessed correlations with measures of circulating lipids, systemic inflammation and adiposity.
METHODS
Systematic review of studies measuring Lp-PLA(2) and at least one of the relevant characteristics in >50 participants.
RESULTS
We identified a total of 77 studies involving 102,499 participants meeting the inclusion criteria. Lp-PLA(2) mass and activity were consistently approximately 10% higher in males than females and 15% higher in Caucasians than African Americans or Hispanics. There were no clear associations of Lp-PLA(2) mass or activity with type II diabetes, markers of systemic inflammation (C-reactive protein, fibrinogen) or with body mass index. Correlations of Lp-PLA(2) mass or activity with low density lipoprotein cholesterol and apolipoprotein B were moderate and positive, whilst correlations with high density lipoprotein cholesterol were negative and moderate to weak. There was no clear differences in associations with any of the above characteristics in groups defined based upon prevalent cardiovascular disease or its risk factors.
CONCLUSIONS
Despite considerable variability in absolute levels of Lp-PLA(2) across studies, the variability of Lp-PLA(2) across gender, ethnicity, and levels of circulating lipids and markers of systemic inflammation are more consistent and appear not to vary importantly across categories defined by CVD or its risk factors.
Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Black or African American; Animals; Apolipoproteins B; Biomarkers; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Female; Humans; Inflammation; Lipids; Male; Risk Factors; Sex Factors; White People
PubMed: 22784637
DOI: 10.1016/j.atherosclerosis.2012.06.020 -
Biomarkers : Biochemical Indicators of... Jun 2012To conduct a comprehensive, systematic review of studies assessing the significance of lipoprotein-associated phospholipase A2 in cardiovascular diseases (CVDs). (Review)
Review
OBJECTIVE
To conduct a comprehensive, systematic review of studies assessing the significance of lipoprotein-associated phospholipase A2 in cardiovascular diseases (CVDs).
MATERIAL AND METHODS
A review of the literature was performed using the search term "Lipoprotein-associated phospholipase A2 (Lp-PLA2)" and each of the following terms: "cardiovascular risk," "cardiovascular death," "atherosclerotic disease," "coronary events," "transient ischemic attack (TIA)," "stroke," and "heart failure." The searches were performed on Medline, Google Scholar and ClinicalTrials.gov.
RESULTS
The majority of published studies showed a significant association between Lp-PLA2 levels and cardiovascular events after multivariate adjustment. The association was consistent across a wide variety of subjects of both sexes and different ethnic backgrounds.
CONCLUSIONS
The role of Lp-PLA2 as a significant biomarker of vascular inflammation was confirmed, and Lp-PLA2 seems to be closely correlated to cardiovascular events. It may be an important therapeutic target and may have an important role in prevention, risk stratification and personalised medicine.
Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Biomarkers; Cardiovascular Diseases; Humans; Inflammation Mediators; Lipoproteins; Molecular Targeted Therapy; Oxidative Stress
PubMed: 22401038
DOI: 10.3109/1354750X.2012.664170 -
North American Journal of Medicine &... Oct 2011Lipoprotein-associated phospholipase A2 (Lp-PLA) is a novel inflammatory biomarker. Basic research has shown that Lp-PLA is involved in the pathogenesis of...
Lipoprotein-associated phospholipase A2 (Lp-PLA) is a novel inflammatory biomarker. Basic research has shown that Lp-PLA is involved in the pathogenesis of atherosclerosis. In the past decade, an increasing number of epidemiological studies have investigated the association of Lp-PLA with atherosclerosis, but its roles in the different stages of atherosclerosis are not established. By undertaking a systematic review of the epidemiological studies on the relationship between Lp-PLA and atherosclerotic cardiovascular disease (CVD)/subclinical atherosclerosis, we tried to evaluate the relationship between Lp-PLA and the different stages of atherosclerosis. MEDLINE, Cochrane Library, and National Knowledge Infrastructure (CNKI) were searched up to September 1st, 2011. The references in all the located articles were manually searched. Epidemiological studies on the association of Lp-PLA with CVD and subclinical atherosclerosis, with total CVD, coronary heart disease (CHD), stroke, and subclinical atherosclerosis as their observation endpoints or outcome variables, were included in this study. Studies which did not assess the hazard ratio (HR), relative risk (RR), or odds ratio (OR) of Lp-PLA or which did not adjust for other known risk factors were excluded. The general information, study design, sample size, outcome variables and their definitions, follow-up duration, Lp-PLA measurements, variables adjusted in the multivariate analysis and main results in the literatures were retrieved. Thirty-nine studies were enrolled in this systematic review. Thirty-three studies (49, 260 subjects) investigated the relationship between Lp-PLA and CVD, among which 31 showed that increased Lp-PLA is associated to high risk for incidence or mortality of CVD: HR/RR per 1 standard deviation (SD) increase = 1.17-1.40; RR for the highest as compared with the lowest quartile was 1.41-3.75 (1.8-2.5 in most studies). Six studies (four cross-sectional studies and two case-control studies, with an overall sample size of 5,537) explored the relationship between Lp-PLA and subclinical atherosclerosis; among them, two studies demonstrated that Lp-PLA was associated with coronary artery calcification in young adults and men. In conclusion, many epidemiological studies have demonstrated that Lp-PLA increases the risk of clinical CVD events. However, whether there is a similar association between Lp-PLA and subclinical atherosclerosis remains unclear. Whether Lp-PLA exerts its effect during the occurrence of clinical events promoted by unstable plaques or at the early stage of atherosclerosis needs to be clarified in further prospective studies.
PubMed: 26339459
DOI: 10.7156/v4i4p201 -
European Journal of Neurology Apr 2012Despite important advances in therapeutic approaches in stroke, the options of acute treatment are still limited. Primary prevention represents another potentially... (Review)
Review
BACKGROUND
Despite important advances in therapeutic approaches in stroke, the options of acute treatment are still limited. Primary prevention represents another potentially highly efficient strategy. For effective prevention the early detection of subjects at risk is of utmost importance. Coinciding with a change in current understanding of atherosclerosis as an inflammatory, cross-organ disease, new parameters to assess the individual risk are emerging.
METHODS
Systematic review of the potential of selected parameters for prediction of cerebrovascular events beyond detection of traditional risk factors that might expand the repertoire of primary prevention programs in stroke.
RESULTS
An absolute carotid intima-media thickness difference of 0.1 mm increases the future risk of stroke by 13-18%. An ankle-brachial index <0.9 was associated with a relative risk of 2.33 (95% CI 2.02-2.68) for stroke. In patients with acute stroke and ABI values < 0.9 the risk for a new vascular event is significantly increased (HR 2.1; 95% CI 1.6-2.8). Measurements of several molecular biomarkers may be used to predict future vascular events independently of traditional risk factors.
CONCLUSIONS
Based on the data presented, there is clear evidence that measurement of the ankle-brachial index identifies subjects of increased stroke risk in primary and secondary care settings as well as of stroke recurrence in acute stroke.
Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Ankle Brachial Index; C-Reactive Protein; Cytokines; Databases, Bibliographic; Fibrinogen; Humans; Inflammation; Risk Factors; Stroke; Tunica Intima; Tunica Media
PubMed: 21895882
DOI: 10.1111/j.1468-1331.2011.03510.x -
Annals of Medicine Aug 2012Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. In the last decades numerous markers have been considered and investigated for the... (Review)
Review
Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. In the last decades numerous markers have been considered and investigated for the prediction of CV events, but only a few of them resulted in improved global risk assessment beyond traditional risk factors when incorporated into coronary evaluation scores. Recent genetic studies have pointed out a few but consistent loci or genes which are independently associated with CV risk. The idea is fascinating that these genetic markers could lead to improved individual CV risk assessment and tailored pharmacological interventions. In this brief review we will not make a systematic review of all non-genetic and genetic markers of CV risk but we will try to make a brief overview of the most interesting ones with the aim to underline potential 'pros' and 'cons' of their implementation in clinical practice.
Topics: Biomarkers; Cardiovascular Diseases; Genetic Markers; Genomics; Humans; Inflammation; Phospholipases; Risk Assessment; Risk Factors
PubMed: 21623699
DOI: 10.3109/07853890.2011.582511 -
Hepatology (Baltimore, Md.) Jun 2011Our objective was to estimate the strength of the effect of the I148M (rs738409 C/G) patatin-like phospholipase domain containing 3 (PNPLA3) variant on nonalcoholic... (Meta-Analysis)
Meta-Analysis Review
Meta-analysis of the influence of I148M variant of patatin-like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease.
UNLABELLED
Our objective was to estimate the strength of the effect of the I148M (rs738409 C/G) patatin-like phospholipase domain containing 3 (PNPLA3) variant on nonalcoholic fatty liver (NAFLD) and disease severity across different populations. We performed a systematic review by a meta-analysis; literature searches identified 16 studies. Our results showed that rs738409 exerted a strong influence not only on liver fat accumulation (GG homozygous showed 73% higher lipid fat content when compared with CC ones, data from 2,937 subjects; P < 1 × 10(-9) ), but also on the susceptibility of a more aggressive disease (GG homozygous had 3.24-fold greater risk of higher necroinflammatory scores and 3.2-fold greater risk of developing fibrosis when compared with CC homozygous; P < 1 × 10(-9) ; data from 1,739 and 2,251 individuals, respectively). Nonalcoholic steatohepatitis (NASH) was more frequently observed in GG than CC homozygous (odds ratio [OR] 3.488, 95% confidence interval [CI] 1.859-6.545, random model; P < 2 × 10(-4) ; data from 2,124 patients). Evaluation of the risk associated with heterozygosity for the variant suggests that the additive genetic model best explains the effect of rs738409 on the susceptibility to develop NAFLD. Nevertheless, carrying two G alleles does not seem to increase the risk of severe histological features. Meta-regression showed a negative correlation between male sex and the effect of rs738409 on liver fat content (slope: -2.45 ± 1.04; P < 0.02). The rs738409 GG genotype versus the CC genotype was associated with a 28% increase in serum alanine aminotransferase levels.
CONCLUSION
By summarizing the amount of evidence, this study provided unequivocal evidence of rs738409 as a strong modifier of the natural history of NAFLD in different populations around the world.
Topics: Adult; Alanine Transaminase; Child; Fatty Liver; Female; Genetic Predisposition to Disease; Heterozygote; Homozygote; Humans; Lipase; Male; Membrane Proteins; Non-alcoholic Fatty Liver Disease; Polymorphism, Single Nucleotide; Severity of Illness Index
PubMed: 21381068
DOI: 10.1002/hep.24283