-
Pharmacogenetics and Genomics Nov 2015Recently, a genome-wide association study showed a statistically significant association between the rs3794087 single nucleotide polymorphism (SNP) in the solute carrier... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND/OBJECTIVE
Recently, a genome-wide association study showed a statistically significant association between the rs3794087 single nucleotide polymorphism (SNP) in the solute carrier family 1--glial affinity glutamate transporter, member 2 (SLC1A2) and the risk for essential tremor (ET). However, four further association studies showed controversial results.We carried out a systematic review and a meta-analysis including all the studies published on the risk of ET related to this SNP.
MATERIALS AND METHODS
The systematic review was performed using several databases, the meta-analysis was carried out using the software Meta-DiSc 1.1.1, and heterogeneity between studies was tested using the Q statistic.
RESULTS
The meta-analysis included five association studies for the SLC1A2 rs3794087 SNP (1925 ET patients, 4914 controls) and the risk for ET. The global diagnostic odds ratio (95% confidence intervals) was 1.08 (0.79-1.48) for the total group. After excluding data from the discovery series (which was responsible for a high degree of heterogeneity), the global diagnostic odds ratio (95% confidence intervals) was 0.96 (0.74-1.23). The separate analysis in White and Asiatic individuals on the frequency of the minor allele of rs3794087 did not show significant differences between ET patients and controls in both subgroups after excluding the discovery series.
CONCLUSION
The results of the meta-analysis suggest that rs3794087 is not associated with the risk for ET.
Topics: Asian People; Case-Control Studies; Essential Tremor; Excitatory Amino Acid Transporter 2; Gene Frequency; Genetic Predisposition to Disease; Genome-Wide Association Study; Glutamate Plasma Membrane Transport Proteins; Humans; Odds Ratio; Polymorphism, Single Nucleotide; Risk Factors; White People
PubMed: 26313486
DOI: 10.1097/FPC.0000000000000171 -
Current Stem Cell Research & Therapy Jul 2012The term tissue engineering is the technology that combines cells, engineering and biological/synthetic material in order to repair, replace or regenerate biological... (Review)
Review
The term tissue engineering is the technology that combines cells, engineering and biological/synthetic material in order to repair, replace or regenerate biological tissues such as bone, muscle, tendons and cartilage. The major human applications of tissue engineering are: skin, bone, cartilage, corneas, blood vessels, left mainstem bronchus and urinary structures. In this systematic review several criteria were identified as the most desirable characteristics of an ideal scaffold. These state that an ideal scaffolds needs to be biodegradable, possess mechanical strength, be highly porous, biocompatible, non-cytotoxic, non antigentic, stuitable for cell attachment, proliferation and differentiation, flexible and elastic, three dimensional, osteoconductive and support the transport of nutrients and metabolic waste. Subsequently, studies reporting on the various advantages and disadvantages of using collagen based scaffolds in musculoskeletal and cartilage tissue engineering were identified. The purpose of this review is to 1) provide a list of ideal characteristics of a scaffold as identified in the literature 2) identify different types of biological protein-based collagen scaffolds used in musculoskeletal and cartilage tissue engineering 3) assess how many of the criteria each scaffold type meets 4) weigh different scaffolds against each other according to their relative properties and shortcomings. The rationale behind this approach is that the ideal scaffold material has not yet been identified. Hence, this review will define how many of the identified ideal characteristics are fulfilled by natural collagen-based scaffolds and address the shortcomings of its use as found in the literature.
Topics: Animals; Cartilage; Collagen; Evaluation Studies as Topic; Guided Tissue Regeneration; Humans; Regenerative Medicine; Stem Cell Transplantation; Tissue Engineering; Tissue Scaffolds
PubMed: 22563667
DOI: 10.2174/157488812800793045 -
American Journal of Medical Genetics.... Sep 2008The serotonin transporter gene (5-HTT) plays a crucial role in serotonergic neurotransmission and has been found to be associated, with varying degrees of significance,... (Meta-Analysis)
Meta-Analysis Review
The serotonin transporter gene (5-HTT) plays a crucial role in serotonergic neurotransmission and has been found to be associated, with varying degrees of significance, with many diseases, including autism. Prior association studies of autism have yielded conflicting results regarding the association between two common 5-HTT polymorphisms, the promoter insertion/deletion (5-HTTLPR) and the intron 2 VNTR (STin2 VNTR). We conducted a systematic review and meta-analysis to test the following hypotheses: (i) there is an association between autism and either or both of the 5-HTTLPR and STin2 VNTR polymorphisms, and (ii) the S allele of 5-HTTLPR and/or the STin2.12 allele of the VNTR are the specific risk alleles for autism. All published family-based and population based studies were examined to determine the overall strength of association between 5-HTT polymorphisms and autism. After exclusion of studies with overlapping samples and studies whose data did not allow for calculation of an odds ratio, 16 studies were included for final analyses, all but two of which used a family-based design. The meta-analysis failed to find a significant overall association between either of the 5-HTT polymorphisms examined and autism. Further, no allelic transmission distortion was found when studies of simplex (11 studies) and multiplex (3 studies) family samples were analyzed separately. However, there was significant heterogeneity by ethnicity; family based studies of US mixed population samples showed preferential transmission of the S allele of 5-HTTLPR (S allele:L allele = 247:183), while there was no allelic distortion among the family-based studies of European and Asian samples.
Topics: Autistic Disorder; DNA Mutational Analysis; Gene Frequency; Haplotypes; Humans; Polymorphism, Genetic; Serotonin Plasma Membrane Transport Proteins
PubMed: 18286633
DOI: 10.1002/ajmg.b.30720 -
European Neuropsychopharmacology : the... Oct 2013There is evidence that 5-HTTLPR is associated with response following treatment from selective serotonin reuptake inhibitors (SSRIs). The short (S) allele has reduced... (Meta-Analysis)
Meta-Analysis Review
There is evidence that 5-HTTLPR is associated with response following treatment from selective serotonin reuptake inhibitors (SSRIs). The short (S) allele has reduced serotonin transporter expression, compared to the long (L) allele, and has been reported to be associated with poorer response in Europeans, with the effect in other populations unclear. However the published literature is inconsistent. A systematic review and meta-analysis was performed to investigate the effect of 5-HTTLPR on discontinuation from antidepressant treatment. Data were obtained from 17 studies including 4309 participants. The principal outcome measure was the allelic odds ratio (OR) for the 5-HTTLPR S allele and discontinuation status. A random effects meta-analysis provided no evidence that the S allele was associated with increased odds of discontinuation from SSRIs in Europeans (OR 1.09, 95% CI 0.83-1.42, p=0.53; 10 studies, n=2504) but in East Asians there was evidence of a reduced odds of discontinuation (OR 0.28, 95% CI 0.12-0.64, p=0.002; 2 studies, n=136). There was a suggestion of small study bias (p=0.05). This meta-analysis provides no evidence of an association between 5-HTTLPR and discontinuation from antidepressant treatment in Europeans. The low number of studies in East Asian samples using SSRIs reduces confidence in our evidence that the S allele decreases the odds of discontinuation in this population. At present, there is no evidence of an association between 5-HTTLPR and discontinuation from SSRI treatment in a European population with further studies required to investigate its effects in different populations.
Topics: Alleles; Antidepressive Agents; Brain; Depression; Drug Resistance; Evidence-Based Medicine; Genetic Association Studies; Genetic Variation; Humans; Nerve Tissue Proteins; Neurons; Randomized Controlled Trials as Topic; Serotonin Plasma Membrane Transport Proteins; Selective Serotonin Reuptake Inhibitors
PubMed: 23265954
DOI: 10.1016/j.euroneuro.2012.12.001 -
Frontiers in Cardiovascular Medicine 2022To assess whether the current body of accumulated data can give convincing evidence in favor of sodium-glucose transport protein-2 inhibitor (SGLT-2i) in all types of...
UNLABELLED
To assess whether the current body of accumulated data can give convincing evidence in favor of sodium-glucose transport protein-2 inhibitor (SGLT-2i) in all types of heart failure (HF). We searched for randomized controlled trials contrasting the effectiveness of SGLT-2i to placebo or other hypoglycemic medications on clinicaltrials.gov, PubMed, and the Cochrane Library database. To gauge effect size, hazard ratios (HR) were employed as measurements. The composite outcome of cardiovascular death or hospitalization owing to HF was the primary endpoint. Eleven studies were included. In comparison to the control group, the data demonstrated that SGLT-2i is related with a decreased incidence of composite outcome (HR: 0.77, 95% CIs: 0.73-0.81, = 0%, < 0.01), CV death (HR: 0.87, 95% CIs: 0.81-0.94, = 3%, < 0.01), all-cause mortality (HR: 0.90, 95% CIs: 0.84-0.96, = 10%, < 0.01), and hospitalization due to HF (HHF) (HR: 0.70, 95% CIs: 0.66-0.75, = 0%, < 0.01). The trial sequential analysis found strong evidence of a decrease in the incidence of all clinical outcomes with SGLT-2i when compared to the control group. Subgroup analysis demonstrated that the association between SGLT-2i and clinical outcome was independent of population characteristics. We confirm that the present evidence supports the use of SGLT-2i in a wide range of HF patients.
SYSTEMATIC REVIEW REGISTRATION
[https://www.crd.york.ac.uk/prospero/#recordDetails], identifier [CRD42022333279].
PubMed: 36531703
DOI: 10.3389/fcvm.2022.1067806 -
Rheumatology International Feb 2012The aim of this study was to explore whether the candidate gene polymorphisms contribute to fibromyalgia susceptibility. The authors conducted a meta-analysis on... (Meta-Analysis)
Meta-Analysis Review
The aim of this study was to explore whether the candidate gene polymorphisms contribute to fibromyalgia susceptibility. The authors conducted a meta-analysis on associations between serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) S/L allele, catechol-O-methltransferase (COMT) val158Met, and serotonin 2A (5-HT2A) receptor 102T/C polymorphisms and fibromyalgia susceptibility as determined using the following: (1) allele contrast, (2) recessive, (3) dominant models, and (4) contrast of homozygotes. We also performed a systematic review with available data of the candidate genes. A total of 21 separate comparisons were considered in this systematic review and meta-analysis. Seventeen candidate genes and over 35 different polymorphisms were identified in studies on fibromyalgia susceptibility. Meta-analysis of the 5-HTTLPR S/L allele and COMT val158Met failed to reveal any association with fibromyalgia. However, meta-analysis of the C allele, CC + CT genotype, and CC versus TT genotype of the 5-HT2A receptor 102T/C polymorphism showed significant association with fibromyalgia. The overall OR of the association between the C allele and fibromyalgia was 1.333 (95% CI = 1.053-1.688, P = 0.017). The ORs for the CC + CT genotype, and CC versus TT genotype showed the same pattern as that observed for the C allele (OR = 1.541, 95% CI = 1.032-2.303, P = 0.035; OR = 1.838, 95% CI = 1.151-2.936, P = 0.011). This meta-analysis demonstrates that the 5-HT2A receptor 102T/C polymorphism confers susceptibility to fibromyalgia. In contrast, no association was found between the 5-HTTLPR S/L allele, COMT val158Met, and susceptibility to fibromyalgia.
Topics: Alleles; Catechol O-Methyltransferase; Fibromyalgia; Genes, Dominant; Genes, Recessive; Genetic Predisposition to Disease; Humans; Polymorphism, Genetic; Receptor, Serotonin, 5-HT2A; Receptors, Neurotransmitter; Serotonin Plasma Membrane Transport Proteins
PubMed: 21120487
DOI: 10.1007/s00296-010-1678-9 -
European Neuropsychopharmacology : the... Oct 2013Suicide is one of the leading causes of death in the world. Its aetiology is complex and diverse, however, epidemiological studies show that suicidal behavior is partly... (Review)
Review
Suicide is one of the leading causes of death in the world. Its aetiology is complex and diverse, however, epidemiological studies show that suicidal behavior is partly heritable. Neurobiological evidence implicates serotonergic dysfunction in suicidality, stimulating genetic research to focus on genes related to the serotonergic system. In this paper, we review evidence from studies examining the association between various serotonergic genes (Tryptophan Hydroxylase genes: TPH1; TPH2, Serotonin Transporter gene: 5-HTTLPR in SLC6A4, Serotonin Receptor genes: HTR1A, HTR2A, HTR1B, HTR2C and Monoamine Oxidase A gene: MAOA) and suicidal behavior. The data show associations between variation on the TPH1 gene and 5-HTTLPR gene and violent suicidal behavior in Caucasian populations, with the least inconsistencies. Results are mixed for the TPH2 gene and serotonin receptor genes, but for some genes, studies that include haplotypic analyses or that examine a larger coding region of the genes tend to provide more reliable results. Findings on endophenotypes of suicidality, such as aggression and impulsivity traits, show positive associations for the TPH1, HTR2A, and MAOA genes, but need further replication, since negative associations are also occasionally reported. Since genes can only partially explain suicidal risk, several studies during the past decade have tried to incorporate environmental factors in the susceptibility model. Studies to date show that variation on the 5-HTTLPR, MAOA and HTR2A gene can interact with stressful life events to increase risk for suicidal behavior. Limitations of case-control studies are discussed and future considerations are put forward with regard to endophenotypic measurements and gene-environment interactions.
Topics: Alleles; Animals; Brain; Case-Control Studies; Endophenotypes; Evidence-Based Medicine; Gene-Environment Interaction; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Variation; Humans; Monoamine Oxidase; Nerve Tissue Proteins; Neurons; Protein Isoforms; Receptors, Serotonin; Self-Injurious Behavior; Serotonin Plasma Membrane Transport Proteins; Tryptophan Hydroxylase; Suicide Prevention
PubMed: 23742855
DOI: 10.1016/j.euroneuro.2013.03.013 -
International Journal of Sport... May 2018Coffee is one of the most consumed beverages in the world, and it can improve insulin sensitivity, stimulating glucose uptake in skeletal muscle when adequate... (Review)
Review
Coffee is one of the most consumed beverages in the world, and it can improve insulin sensitivity, stimulating glucose uptake in skeletal muscle when adequate carbohydrate intake is observed. The aim of this review is to analyze the effects of coffee and coffee components on muscle glycogen metabolism. A literature search was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis, and seven studies were included, that explored the effects of coffee components on various substances and signaling proteins. In one of the studies with humans, caffeine was shown to increase glucose levels, Ca/calmodulin-dependent protein kinase phosphorylation, glycogen resynthesis rates, and glycogen accumulation after exercise. After intravenous injection of caffeine in rats, caffeine increased adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation, and glucose transport. In in vitro studies, caffeine raised AMPK and ACC phosphorylation, increasing glucose transport activity and reducing energy status in rat muscle cells. Cafestol and caffeic acid increased insulin secretion in rat beta cells and glucose uptake into human muscle cells. Caffeic acid also increased AMPK and ACC phosphorylation, reducing the energy status and increasing glucose uptake in rat muscle cells. Chlorogenic acid did not show any positive or negative effect. The findings from this review must be taken with caution due to the limited number of studies on the subject. In conclusion, various coffee components had a neutral or positive role in the metabolism of glucose and muscle glycogen, whereas no detrimental effect was described. Coffee beverages should be tested as an option for athletes' glycogen recovery.
Topics: AMP-Activated Protein Kinases; Acetyl-CoA Carboxylase; Animals; Coffee; Exercise; Glycogen; Humans; Insulin Resistance; Insulin-Secreting Cells; Muscle Cells; Muscle, Skeletal; Phosphorylation; Rats
PubMed: 29345166
DOI: 10.1123/ijsnem.2017-0342 -
Journal of Sports Sciences Feb 2020High-intensity-interval-training (HIIT) has been suggested to have beneficial effects in multiple populations across individual systematic reviews, although there is a... (Meta-Analysis)
Meta-Analysis
High-intensity-interval-training (HIIT) has been suggested to have beneficial effects in multiple populations across individual systematic reviews, although there is a lack of clarity in the totality of the evidence whether HIIT is effective and safe across different populations and outcomes. The aim of this meta-review was to establish the benefits, safety and adherence of HIIT interventions across all populations from systematic reviews and meta-analyses. Major databases were searched for systematic reviews (with/without meta-analyses) of randomised & non-randomised trials that compared HIIT to a control. Thirty-three systematic reviews (including 25 meta-analyses) were retrieved encompassing healthy subjects and people with physical health complications. Evidence suggested HIIT improved cardiorespiratory fitness, anthropometric measures, blood glucose and glycaemic control, arterial compliance and vascular function, cardiac function, heart rate, some inflammatory markers, exercise capacity and muscle mass, versus non-active controls. Compared to active controls, HIIT improved cardiorespiratory fitness, some inflammatory markers and muscle structure. Improvements in anxiety and depression were seen compared to pre-training. Additionally, no acute injuries were reported, and mean adherence rates surpassed 80% in most systematic reviews. Thus, HIIT is associated with multiple benefits. Further large-scale high-quality studies are needed to reaffirm and expand these findings. ACSM: American College of Sports Medicine; BMI: Body Mass Index; BNP: Brain Natriuretic Peptide; BP: Blood Pressure; CAD: Coronary Artery Disease; CHD: Coronary Heart Disease; COPD: Chronic Obstructive Pulmonary Disease; CRP: c- reactive Protein; CVD: Cardiovascular Disease; DBP: Diastolic Blood Pressure; ES: Effect Size; FAS: Reduced Fatty Acid Synthase; FATP-1: Reduced Fatty Acid Transport Protein 1; FMD: Flow Mediated Dilation; Hs-CRP: High-sensitivity c- reactive Protein; HDL: High Density Lipoprotein; HIIT: High-Intensity Interval Training; HOMA: Homoeostatic Model Assessment; HR: Heart Rate; HTx: Heart Transplant Recipients; IL-6: Interleukin-6; LDL: Low Density Lipoprotein; LV: Left Ventricular; LVEF: Left Ventricular Ejection Fraction; MD: Mean Difference; MetS: Metabolic Syndrome; MPO: Myeloperoxidase; MICT: Moderate-Intensity Continuous Training; NO: Nitric Oxide; NRCT: Non-Randomised Controlled Trial; PA: Physical Activity; PAI-1: Plasminogen-activator-inhibitor-1; QoL: Quality of Life; RCT: Randomised Controlled Trial; RoB: Risk of Bias; RPP: Rate Pressure Product; RT: Resistance Training; SBP: Systolic Blood Pressure; SD: Standardised Difference; SMD: Standardised Mean Difference; TAU: Treatment-As-Usual; T2DM: Type 2 Diabetes Mellitus; TC: Total Cholesterol; TG: Triglycerides; TNF-alfa: Tumour Necrosis Factor alpha; UMD: Unstandardised Mean Difference; WC: Waist Circumference; WHR: Waist-to-Hip Ratio; WMD: Weighted Mean Difference: HIIT may improve cardiorespiratory fitness, cardiovascular function, anthropometric variables, exercise capacity, muscular structure and function, and anxiety and depression severity in healthy individuals and those with physical health disorders.Additionally, HIIT appears to be safe and does not seem to be associated with acute injuries or serious cardiovascular events.
Topics: Anthropometry; Anxiety; Biomarkers; Cardiorespiratory Fitness; Depression; Exercise Tolerance; High-Intensity Interval Training; Humans; Inflammation; Mental Health; Muscle, Skeletal; Quality of Life
PubMed: 31889469
DOI: 10.1080/02640414.2019.1706829 -
PloS One 20145-Hydroxytryptamine receptor (5-HTR) and 5-hydroxytryptamine transporter (5-HTT) gene polymorphisms have been reported to be associated with susceptibility to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
5-Hydroxytryptamine receptor (5-HTR) and 5-hydroxytryptamine transporter (5-HTT) gene polymorphisms have been reported to be associated with susceptibility to obstructive sleep apnea syndrome (OSAS). The associations, derived from sporadic, inconsistent, small-sample-size studies, need to be evaluated further in a meta-analysis.
METHODS
Relevant studies were identified by searching PubMed, Embase, The Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, and Weipu. Eligible data were extracted from each included study. Odds ratios (ORs) were calculated using a fixed-effects or a random-effects model. The ORs and 95% confidence interval (CI) were used to assess the strength of the association between serotonergic gene polymorphisms and OSAS in the dominant and recessive models, as well as alleles. The Q statistic was used to evaluate homogeneity and Begg's test was used to assess publication bias.
RESULTS
Eight studies were finally included in the meta-analysis of the association between 5-HTR2A gene variants (including 102T/C and 1438G/A), 5-HTT gene polymorphisms (including 5-HTT gene-linked promoter region (5-HTTLRP), and serotonin transporter intron 2 variable number tandem repeat (STin2VNTR) and OSAS risk. The G allele of 5-HTR2A 1438G/A, long 5-HTTLPR, and 10-tandem-repeats STin2VNTR were shown to increase OSAS susceptibility, with ORs of 2.33 (A vs. G, 95% CI 1.48-3.66), 1.24 (L vs. S, 95% CI: 1.04-1.49), and 2.87 (10 vs. 12, 95% CI: 1.38-5.97), respectively. These significant differences were determined in both dominant and recessive models. Of the 5-HTR2A 1438G/A gene polymorphism, the AA genotype increased the OSAS risk, with an OR of 4.21 (95% CI: 2.83-6.25) in a recessive model in male OSAS patients, but no significant association was found in females.
CONCLUSIONS
Our meta-analysis demonstrated that polymorphisms in the 5-HTR2A 1438G/A and 5-HTT genes contributed to susceptibility to OSAS. The A allele of the 1438G/A gene polymorphism is predominantly distributed in males and increased the OSAS risk significantly.
Topics: Female; Genetic Association Studies; Humans; Male; Receptor, Serotonin, 5-HT2A; Serotonin Plasma Membrane Transport Proteins; Sex Factors; Sleep Apnea, Obstructive
PubMed: 24475124
DOI: 10.1371/journal.pone.0086460