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Epilepsy & Behavior : E&B Jul 2014The association between the C3435T polymorphism in the MDR1 gene and refractory epilepsy remains controversial. The association appears to be influenced by ethnicity and... (Meta-Analysis)
Meta-Analysis Review
The association between the C3435T polymorphism in the MDR1 gene and refractory epilepsy remains controversial. The association appears to be influenced by ethnicity and region. We have performed a systematic review and meta-analysis to assess the link between the MDR1 C3435T polymorphism and refractory epilepsy in the Chinese population. We searched the Cochrane Library, MIDLINE, EMBASE, CBM disc, CNKI, VIP, and WANFANG databases for literature published through August 2013 for case-control studies that evaluated the association between the MDR1 C3435T polymorphism and refractory epilepsy. Twenty-one case-control studies involving 4269 patients (1863 cases in the group with drug-resistant epilepsy and 2406 in the group with drug-responsive epilepsy) were included in the systematic review and meta-analysis. The analysis showed that there were significantly more cases with the MDR1 3435 CC genotype in the group with drug-resistant epilepsy than in the group with drug-responsive epilepsy [odds ratio (OR)=1.50, 95% confidence interval (CI)=1.09-2.06, P=0.01]. In a subanalysis of patients from the southern regions of China, the correlation was not significant [odds ratio (OR)=1.2, 95% confidence interval (CI)=0.89-1.64, P=0.24]. The relationship established in a subset of the Chinese population between the MDR1 C3435T polymorphism and refractory epilepsy will guide epilepsy treatment and development of new AEDs.
Topics: ATP Binding Cassette Transporter, Subfamily B; Asian People; Databases, Factual; Epilepsy; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Polymorphism, Single Nucleotide
PubMed: 24953225
DOI: 10.1016/j.yebeh.2014.05.007 -
Biochemical Pharmacology Feb 2022Cholesterol esterification proteins Sterol-O acyltransferases (SOAT) 1 and 2 are emerging prognostic markers in many cancers. These enzymes utilise fatty acids... (Meta-Analysis)
Meta-Analysis
Cholesterol esterification proteins Sterol-O acyltransferases (SOAT) 1 and 2 are emerging prognostic markers in many cancers. These enzymes utilise fatty acids conjugated to coenzyme A to esterify cholesterol. Cholesterol esterification is tightly regulated and enables formation of lipid droplets that act as storage organelles for lipid soluble vitamins and minerals, and as cholesterol reservoirs. In cancer, this provides rapid access to cholesterol to maintain continual synthesis of the plasma membrane. In this systematic review and meta-analysis, we summarise the current depth of understanding of the role of this metabolic pathway in pan-cancer development. A systematic search of PubMed, Scopus, Web of Science, and Cochrane Library for preclinical studies identified eight studies where cholesteryl ester concentrations were compared between tumour and adjacent-normal tissue, and 24 studies where cholesterol esterification was blocked by pharmacological or genetic approaches. Tumour tissue had a significantly greater concentration of cholesteryl esters than non-tumour tissue (p < 0.0001). Pharmacological or genetic inhibition of SOAT was associated with significantly smaller tumours of all types (p ≤ 0.002). SOAT inhibition increased tumour apoptosis (p = 0.007), CD8 + lymphocyte infiltration and cytotoxicity (p ≤ 0.05), and reduced proliferation (p = 0.0003) and metastasis (p < 0.0001). Significant risk of publication bias was found and may have contributed to a 32% overestimation of the meta-analysed effect size. Avasimibe, the most frequently used SOAT inhibitor, was effective at doses equivalent to those previously reported to be safe and tolerable in humans. This work indicates that SOAT inhibition should be explored in clinical trials as an adjunct to existing anti-neoplastic agents.
Topics: Animals; Anticholesteremic Agents; Antineoplastic Agents; Cholesterol; Clinical Trials as Topic; Esterification; Humans; Organic Anion Transporters; Tumor Burden; Urea; Xenograft Model Antitumor Assays
PubMed: 34407453
DOI: 10.1016/j.bcp.2021.114731 -
Scientific Reports Apr 2022The cluster of differentiation 36 (CD36) is one of the main receptors implicated in the pathogenesis of the cardiovascular disease. This study aimed to assess the... (Meta-Analysis)
Meta-Analysis
The cluster of differentiation 36 (CD36) is one of the main receptors implicated in the pathogenesis of the cardiovascular disease. This study aimed to assess the association between CD36 rs1761667 polymorphism and cardiometabolic risk factors including body mass index (BMI), waist circumference (WC), total cholesterol (TC), triglyceride, HDL-C, LDL-C, blood pressure and fasting blood glucose (FBG). PubMed, EMBASE, Scopus, web of science, and Google Scholar were searched up to December 2021. Subgroup and meta-regression analyses were conducted to explore sources of heterogeneity. Eighteen eligible studies (6317 participants) were included in the study. In the overall analysis, a significant association was found between rs1761667 polymorphism of CD36 and TG in allelic (p < 0.001), recessive (p = 0.001) and homozygous (p = 0.006) models. A relationship between this polymorphism and HDL-C and FBG level was observed in the recessive genetic model. In the subgroup analysis, the A allele was associated with impaired lipid profiles (TC, LDL-C and HDL-C) in the Asian population. The influences of health status, design of the study, confounders, and other sources of heterogeneity should be considered when interpreting present findings. Cohort studies with large sample size and in different ethnicities are needed to confirm the relationship between rs1761667 SNP and cardiometabolic risk factors.
Topics: Adult; Blood Pressure; CD36 Antigens; Cardiometabolic Risk Factors; Cardiovascular Diseases; Cholesterol, LDL; Humans; Risk Factors; Waist Circumference
PubMed: 35396566
DOI: 10.1038/s41598-022-09908-0 -
Bipolar Disorders Nov 2010Antidepressant-induced mania (AIM) has been associated with the serotonin-transporter-linked promoter region (5-HTTLPR) polymorphism in some studies but not in others.... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Antidepressant-induced mania (AIM) has been associated with the serotonin-transporter-linked promoter region (5-HTTLPR) polymorphism in some studies but not in others. We conducted a meta-analysis of those studies and other studies of genetic predictors of AIM.
METHODS
MEDLINE-based searches of genetic studies of AIM were conducted, and a meta-analysis of six studies of 5-HTTLPR was performed. Other polymorphisms were insufficiently studied to allow for meta-analysis.
RESULTS
There was an association of the short (s) variant of 5-HTTLPR and AIM [risk ratio (RR) = 1.35, 95% confidence interval (CI): 1.04-1.76, p=0.02]. There was a higher frequency of s carriers (sl and ss genotypes) in those who developed AIM [RR = 1.38, 95% CI: 0.98-1.93), p=0.06].
CONCLUSION
The 5-HTTLPR polymorphism appears to have a moderate effect size association with AIM in patients with bipolar disorder.
Topics: Antidepressive Agents; Bipolar Disorder; Humans; MEDLINE; Pharmacogenetics; Polymorphism, Genetic; Serotonin Plasma Membrane Transport Proteins
PubMed: 21040287
DOI: 10.1111/j.1399-5618.2010.00864.x -
Journal of Psychiatric Research Jan 2017To summarize and synthesize the growing gene x environment (GxE) research investigating the promoter region of the serotonin transporter gene (5-HTTLPR) in the eating... (Meta-Analysis)
Meta-Analysis Review
A systematic review and secondary data analysis of the interactions between the serotonin transporter 5-HTTLPR polymorphism and environmental and psychological factors in eating disorders.
OBJECTIVES
To summarize and synthesize the growing gene x environment (GxE) research investigating the promoter region of the serotonin transporter gene (5-HTTLPR) in the eating disorders (ED) field, and overcome the common limitation of low sample size, by undertaking a systematic review followed by a secondary data meta-analysis of studies identified by the review.
METHOD
A systematic review of articles using PsycINFO, PubMed, and EMBASE was undertaken to identify studies investigating the interaction between 5-HTTLPR and an environmental or psychological factor, with an ED-related outcome variable. Seven studies were identified by the systematic review, with complete data sets of five community (n = 1750, 64.5% female) and two clinical (n = 426, 100% female) samples combined to perform four secondary-data analyses: 5-HTTLPR x Traumatic Life Events to predict ED status (n = 909), 5-HTTLPR x Sexual and Physical Abuse to predict bulimic symptoms (n = 1097), 5-HTTLPR x Depression to predict bulimic symptoms (n = 1256), and 5-HTTLPR x Impulsiveness to predict disordered eating (n = 1149).
RESULTS
Under a multiplicative model, the low function (s) allele of 5-HTTLPR interacted with traumatic life events and experiencing both sexual and physical abuse (but not only one) to predict increased likelihood of an ED and bulimic symptoms, respectively. However, under an additive model there was also an interaction between sexual and physical abuse considered independently and 5-HTTLPR, and no interaction with traumatic life events. No other GxE interactions were significant.
CONCLUSION
Early promising results should be followed-up with continued cross-institutional collaboration in order to achieve the large sample sizes necessary for genetic research.
Topics: Feeding and Eating Disorders; Gene-Environment Interaction; Genetic Predisposition to Disease; Humans; Serotonin Plasma Membrane Transport Proteins
PubMed: 27701012
DOI: 10.1016/j.jpsychires.2016.09.023 -
Neuropsychopharmacology : Official... Mar 2022Ondansetron is a selective serotonin (5HT3) receptor antagonist that is under evaluation as an adjunctive treatment for schizophrenia, and a novel treatment for...
Ondansetron is a selective serotonin (5HT3) receptor antagonist that is under evaluation as an adjunctive treatment for schizophrenia, and a novel treatment for hallucinations in Parkinson's disease. Ondansetron reverses sensory gating deficits and improves visuoperceptual processing in animal models of psychosis, but it is unclear to what extent preclinical findings have been replicated in humans. We systematically reviewed human studies that evaluated the effects of ondansetron and other 5HT3 receptor antagonists on sensory gating deficits or sensory processing. Of 11 eligible studies, eight included patients with schizophrenia who were chronically stable on antipsychotic medication; five measured sensory gating using the P50 suppression response to a repeated auditory stimulus; others included tests of visuoperceptual function. Three studies in healthy participants included tests of visuoperceptual and sensorimotor function. A consistent and robust finding (five studies) was that ondansetron and tropisetron (5HT3 antagonist and α7-nicotinic receptor partial agonist) improved sensory gating in patients with schizophrenia. Tropisetron also improved sustained visual attention in non-smoking patients. There was inconsistent evidence of the effects of 5HT3 antagonists on other measures of sensory processing, but interpretation was limited by the small number of studies, methodological heterogeneity and the potential confounding effects of concomitant medication in patients. Despite these limitations, we found strong evidence that selective 5HT3 antagonists (with or without direct α7-nicotinic partial agonist effects) improved sensory gating. Future studies should investigate how this relates to potential improvement in neurocognitive symptoms in antipsychotic naive patients with prodromal or milder symptoms, in order to understand the clinical implications.
Topics: Antipsychotic Agents; Humans; Perception; Schizophrenia; Sensory Gating; alpha7 Nicotinic Acetylcholine Receptor
PubMed: 35017671
DOI: 10.1038/s41386-021-01255-4 -
The Pharmacogenomics Journal Jun 2021This meta-analysis was conducted to determine the genotypic effects of rs4149056 and rs2306283 polymorphism in SLCO1B1 gene on myopathy in patients with statin. Studies... (Meta-Analysis)
Meta-Analysis
This meta-analysis was conducted to determine the genotypic effects of rs4149056 and rs2306283 polymorphism in SLCO1B1 gene on myopathy in patients with statin. Studies were searched using multiple databases and selected following inclusion criteria. Two reviewers independently performed data extraction and assessments for risk of bias. Fixed-or-random-effect was applied to pool allele frequency/effects. Mixed-effect logit model was used to pool genotypic effects using individual patient data. Heterogeneity and publication bias were explored. Fourteen studies were pooled for rs4149056; the minor C allele frequency were 15% in Caucasians and 14% in Asians. Six studies were pooled for rs2306283; the minor G allele frequency was 34% in Caucasian and 75% in Asians. Genotypic effects of rs4149056 polymorphism in Caucasians indicated that statin users who carried CC and TC genotypes had a significantly higher risk of myopathy than those who carried TT genotype, with a pooled odds ratio (OR) of 2.9 (95% confidence interval, 1.59, 5.34) and 1.6 (1.20, 2.16), respectively. For subgroup analysis, CC and TC genotypes also suggested a higher risk of myopathy in simvastatin users [OR = 2.8 (1.17, 6.77) and OR = 1.8 (1.15, 2.77), respectively] and in atorvastatin users [OR = 4.0 (1.23, 12.63) and OR = 2.0 (1.11, 3.52), respectively] than those who carried TT genotype. There was no significant association between rs2306283 polymorphism and myopathy in Caucasians and Asians. There was no evidence of publication bias for both polymorphisms.
Topics: Animals; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Liver-Specific Organic Anion Transporter 1; Muscular Diseases
PubMed: 33608664
DOI: 10.1038/s41397-021-00208-w -
Diabetes, Obesity & Metabolism Jul 2020To compare the efficacy and tolerability of sodium-glucose co-transporter 2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in adults with... (Meta-Analysis)
Meta-Analysis Review
AIM
To compare the efficacy and tolerability of sodium-glucose co-transporter 2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in adults with type 2 diabetes.
MATERIALS AND METHODS
Electronic databases were searched from inception to 24 April 2019 for randomized controlled trials reporting change in glycated haemoglobin (HbA1c) at approximately 24 and/or 52 weeks for SGLT-2is and/or GLP-1RAs (classified as short- and long-acting). Bayesian network meta-analyses were conducted to compare within and between SGLT-2i and GLP-1RA classes for cardiometabolic efficacy and adverse events (PROSPERO registration number: CRD42018091306).
RESULTS
Sixty-four trials (53 trials of 24 weeks; seven trials of 52 weeks; four trials of both 24 and 52 weeks), comprising 31 384 participants were identified. Compared with placebo, all treatments improved HbA1c. Long-acting GLP-1RAs reduced HbA1c compared with short-acting GLP-1RAs and SGLT-2is, with semaglutide showing greater reduction compared with placebo [24 weeks: -1.49% (95% credible interval: -1.76, -1.22); 52 weeks: -1.38% (-2.05, -0.71)] and all other treatments. Long-acting GLP-1RAs showed benefits in body weight and waist circumference reduction, while SGLT-2is reduced blood pressure. SGLT-2is showed increased risk of genital infection in comparison with long-acting GLP-1RAs [odds ratio (95% credible interval): 5.26 (1.45, 25.00)], while GLP-1RAs showed increased risk of diarrhoea in comparison with SGLT-2is [short-acting GLP-1RAs: 1.65 (1.09, 2.49); long-acting GLP-1RAs: 2.23 (1.51, 3.28)]. No other differences were found between SGLT-2is and GLP-1RAs in adverse events.
CONCLUSION
Long-acting GLP-1RAs showed superiority in reducing HbA1c levels, body weight and waist circumference. SGLT-2is showed reductions in blood pressure levels. This review provides essential evidence to guide treatment recommendations in the management of type 2 diabetes.
Topics: Bayes Theorem; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Glucose; Humans; Hypoglycemic Agents; Network Meta-Analysis; Sodium; Sodium-Glucose Transporter 2 Inhibitors; Symporters
PubMed: 32077218
DOI: 10.1111/dom.14008 -
Implementation Science : IS Jul 2022Many strategies aimed at deprescribing benzodiazepine receptor agonists (BZRA) in older adults have already been evaluated with various success rates. There is so far no... (Review)
Review
Barriers and enablers for deprescribing benzodiazepine receptor agonists in older adults: a systematic review of qualitative and quantitative studies using the theoretical domains framework.
BACKGROUND
Many strategies aimed at deprescribing benzodiazepine receptor agonists (BZRA) in older adults have already been evaluated with various success rates. There is so far no consensus on which strategy components increase deprescribing the most. Yet, despite an unfavourable benefit-to-risk ratio, BZRA use among older adults remains high. We systematically reviewed barriers and enablers for BZRA deprescribing in older adults.
METHODS
Two reviewers independently screened records identified from five electronic databases-Medline, Embase, PsycINFO, CINAHL and the Cochrane library-and published before October 2020. They searched for grey literature using Google Scholar. Qualitative and quantitative records reporting data on the attitudes of older adults, caregivers and healthcare providers towards BZRA deprescribing were included. Populations at the end of life or with specific psychiatric illness, except for dementia, were excluded. The two reviewers independently assessed the quality of the included studies using the mixed-methods appraisal tool. Barriers and enablers were identified and then coded into domains of the theoretical domains framework (TDF) using a combination of deductive and inductive qualitative analysis. The most relevant TDF domains for BZRA deprescribing were then identified.
RESULTS
Twenty-three studies were included 13 quantitative, 8 qualitative and 2 mixed-method studies. The points of view of older adults, general practitioners and nurses were reported in 19, 9 and 3 records, respectively. We identified barriers and enablers in the majority of TDF domains and in two additional themes: "patient characteristics" and "BZRA prescribing patterns". Overall, the most relevant TDF domains were "beliefs about capabilities", "beliefs about consequences", "environmental context and resources", "intention", "goals", "social influences", "memory, attention and decision processes". Perceived barriers and enablers within domains differed across settings and across stakeholders.
CONCLUSION
The relevant TDF domains we identified can now be linked to behavioural change techniques to help in the design of future strategies and health policies. Future studies should also assess barriers and enablers perceived by under-evaluated stakeholders (such as pharmacists, psychiatrists and health care professionals in the hospital setting).
TRIAL REGISTRATION
This work was registered on PROSPERO under the title "Barriers and enablers to benzodiazepine receptor agonists deprescribing".
REGISTRATION NUMBER
CRD42020213035.
Topics: Aged; Deprescriptions; General Practitioners; Humans; Intention; Pharmacists; Qualitative Research; Receptors, GABA-A
PubMed: 35804428
DOI: 10.1186/s13012-022-01206-7 -
Molecular Psychiatry Oct 2016l-type calcium channel (LTCC) antagonists have been used in bipolar disorder for over 30 years, without becoming an established therapeutic approach. Interest in this... (Review)
Review
l-type calcium channel (LTCC) antagonists have been used in bipolar disorder for over 30 years, without becoming an established therapeutic approach. Interest in this class of drugs has been rekindled by the discovery that LTCC genes are part of the genetic aetiology of bipolar disorder and related phenotypes. We have therefore conducted a systematic review of LTCC antagonists in the treatment and prophylaxis of bipolar disorder. We identified 23 eligible studies, with six randomised, double-blind, controlled clinical trials, all of which investigated verapamil in acute mania, and finding no evidence that it is effective. Data for other LTCC antagonists (diltiazem, nimodipine, nifedipine, methyoxyverapamil and isradipine) and for other phases of the illness are limited to observational studies, and therefore no robust conclusions can be drawn. Given the increasingly strong evidence for calcium signalling dysfunction in bipolar disorder, the therapeutic candidacy of this class of drugs has become stronger, and hence we also discuss issues relevant to their future development and evaluation. In particular, we consider how genetic, molecular and pharmacological data can be used to improve the selectivity, efficacy and tolerability of LTCC antagonists. We suggest that a renewed focus on LTCCs as targets, and the development of 'brain-selective' LTCC ligands, could be one fruitful approach to innovative pharmacotherapy for bipolar disorder and related phenotypes.
Topics: Bipolar Disorder; Calcium Channel Blockers; Calcium Channels, L-Type; Double-Blind Method; Humans; Isradipine; Nimodipine; Verapamil
PubMed: 27240535
DOI: 10.1038/mp.2016.86