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Neuroscience and Biobehavioral Reviews Sep 2023Recent lifestyle changes have resulted in tremendous peer pressure and mental stress, and increased the incidences of chronic psychological disorders; like addiction,... (Review)
Review
Recent lifestyle changes have resulted in tremendous peer pressure and mental stress, and increased the incidences of chronic psychological disorders; like addiction, depression and anxiety (ADA). In this context, the stress-tolerance levels vary amongst individuals and genetic factors play prominent roles. Vulnerable individuals may often be drawn towards drug-addiction to combat stress. This systematic review critically appraises the relationship of various genetic factors linked with the incidences of ADA development. For coherence, we focused solely on cocaine as a substance of abuse in this study. Online scholarly databases were used to screen pertinent literature using apt keywords; and the final retrieval included 42 primary-research articles. The major conclusion drawn from this systematic analysis states that there are 51 genes linked with the development of ADA; and 3 (BDNF, PERIOD2 and SLC6A4) of them are common to all the three aspects of ADA. Further, inter-connectivity analyses of the 51 genes further endorsed the central presence of BDNF and SLC6A4 genes in the development of ADA disorders. The conclusions derived from this systematic study pave the way for future studies for the identification of diagnostic biomarkers and drug targets; and for the development of novel and effective therapeutic regimens against ADA.
Topics: Humans; Cocaine-Related Disorders; Depression; Brain-Derived Neurotrophic Factor; Anxiety; Anxiety Disorders; Cocaine; Serotonin Plasma Membrane Transport Proteins
PubMed: 37271299
DOI: 10.1016/j.neubiorev.2023.105270 -
Molecular Pain 2021Trigeminal neuralgia (TN) is a severe facial pain disease of unknown cause and unclear genetic background. To examine the existing knowledge about genetics in TN, we...
Trigeminal neuralgia (TN) is a severe facial pain disease of unknown cause and unclear genetic background. To examine the existing knowledge about genetics in TN, we performed a systematic study asking about the prevalence of familial trigeminal neuralgia, and which genes that have been identified in human TN studies and in animal models of trigeminal pain. MedLine, Embase, Cochrane Library and Web of Science were searched from inception to January 2021. 71 studies were included in the systematic review. Currently, few studies provide information about the prevalence of familial TN; the available evidence indicates that about 1-2% of TN cases have the familial form. The available human studies propose the following genes to be possible contributors to development of TN: CACNA1A, CACNA1H, CACNA1F, KCNK1, TRAK1, SCN9A, SCN8A, SCN3A, SCN10A, SCN5A, NTRK1, GABRG1, MPZ gene, MAOA gene and SLC6A4. Their role in familial TN still needs to be addressed. The experimental animal studies suggest an emerging role of genetics in trigeminal pain, though the animal models may be more relevant for trigeminal neuropathic pain than TN per se. In summary, this systematic review suggests a more important role of genetic factors in TN pathogenesis than previously assumed.
Topics: Animals; Facial Pain; Humans; NAV1.7 Voltage-Gated Sodium Channel; Serotonin Plasma Membrane Transport Proteins; Trigeminal Neuralgia
PubMed: 34000891
DOI: 10.1177/17448069211016139 -
Frontiers in Genetics 2019Vitamin-D binding protein (DBP) also known as GC protein, is a major determinant for vitamin- D metabolism and transport. GC1F, GC1S, and GC2 are the three allelic...
Vitamin-D binding protein (DBP) also known as GC protein, is a major determinant for vitamin- D metabolism and transport. GC1F, GC1S, and GC2 are the three allelic variants (denoted as rs4588 and rs7041) of GC, and known to be associated with chronic obstructive pulmonary disease (COPD). However, contradictory reports and population specific risk attributed by these alleles warranted detailed genetic epidemiology study to establish the association between GC variants and COPD. In this study we performed a meta-analysis and investigated the genetic architecture of GC locus to establish the association and uncover the plausible reason for allelic heterogeneity. Published cross-sectional case control studies were screened and meta-analysis was performed between GC variants and COPD outcome. RevMan-v5.3 software was used to perform random and/or fixed models to calculate pooled odds ratio (Meta-OR). Linkage disequilibrium (LD) and haplotypes at GC locus were evaluated using 1000 Genomes genotype data. functional implications of rs4588 and rs7041 was tested using publicly available tools. GC1F allele and GC1F/1F genotype were found to confer COPD risk in overall meta-analysis. GC1S/1S was found to confer risk only among Europeans. investigation of rs4588 and rs7041 identified strong eQTL effects and potential role in regulation of GC expression. Large differences in allele frequencies, linkage disequilibrium (LD) and haplotypes were identified at GC locus across different populations (Japanese, African, Europeans, and Indians), which may explain the variable association of different GC alleles in different populations. GC1F and GC1F/1F impose significant genetic risk for COPD, among Asians. Considerable differences in allele frequencies and LD structure in GC locus may impose population specific risk.
PubMed: 31156695
DOI: 10.3389/fgene.2019.00413 -
PloS One Jan 2011Natural resistance associated macrophage protein 1 (NRAMP1), encoded by the SLC11A1 gene, has been described to regulate macrophage activation and be associated with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Natural resistance associated macrophage protein 1 (NRAMP1), encoded by the SLC11A1 gene, has been described to regulate macrophage activation and be associated with infectious and autoimmune diseases. The relation between SLC11A1 polymorphisms and tuberculosis susceptibility has been studied in different populations.
METHODS
We systematically reviewed published studies on SLC11A1 polymorphisms and tuberculosis susceptibility until September 15, 2010 and quantitatively summarized associations of the most widely studied polymorphisms using meta-analysis.
RESULTS
In total, 36 eligible articles were included in this review. In Meta-analysis, significant associations were observed between tuberculosis risk and widely studied SLC11A1 polymorphisms with summarized odds ratio of 1.35 (95%CI, 1.17-1.54), 1.25 (95% CI, 1.04-1.50), 1.23 (95% CI, 1.04-1.44), 1.31 (95%CI, 1.08-1.59) for 3' UTR, D543N, INT4, and 5' (GT)n, respectively. Heterogeneity between studies was not pronounced, and the associations did not remarkably vary in the stratified analysis with respect to study population and study base.
CONCLUSIONS
The association between SLC11A1 polymorphisms and tuberculosis susceptibility observed in our analyses supports the hypothesis that NRAMP1 might play an important role in the host defense to the development of tuberculosis.
Topics: Cation Transport Proteins; Genetic Predisposition to Disease; Humans; Polymorphism, Genetic; Tuberculosis
PubMed: 21283567
DOI: 10.1371/journal.pone.0015831 -
Drug Design, Development and Therapy 2018The aim of this study was to summarize the characteristics, efficacy, and safety of vesicular monoamine transporter-2 (VMAT-2) inhibitors for treating tardive dyskinesia... (Meta-Analysis)
Meta-Analysis Review
AIM
The aim of this study was to summarize the characteristics, efficacy, and safety of vesicular monoamine transporter-2 (VMAT-2) inhibitors for treating tardive dyskinesia (TD).
MATERIALS AND METHODS
We conducted a literature search in PubMed, Cochrane Database, and ClinicalTrials.gov, screening for systematic reviews, meta-analyses or double-blind, randomized, placebo-controlled trials (DBRPCTs) reporting efficacy or safety data of VMAT-2 inhibitors (tetrabenazine, deutetrabenazine, and valbenazine) in patients with TD. A random effects meta-analysis of efficacy and safety data from DBRPCTs was performed.
RESULTS
Two acute, 12-week DBRPCTs with deutetrabenazine 12-48 mg/day (n=413) and 4 acute, 4-6-week double-blind trials with valbenazine 12.5-100 mg/day (n=488) were meta-analyzable, without meta-analyzable, high-quality data for tetrabenazine. Regarding reduction in total Abnormal Involuntary Movement Scale (AIMS) scores (primary outcome), both deutetrabenazine (k=2, n=413, standardized mean difference [SMD] =-0.40, 95% confidence interval [CI] =-0.19, -0.62, <0.001; weighted mean difference (WMD) =-1.44, 95% CI =-0.67, -2.19, <0.001) and valbenazine (k=4, n=421, SMD =-0.58, 95% CI =-0.26, -0.91, <0.001; WMD =-2.07, 95% CI =-1.08, -3.05, <0.001) significantly outperformed placebo. Results were confirmed regarding responder rates (≥50% AIMS total score reduction; deutetrabenazine: risk ratio [RR] =2.13, 95% CI =1.10, 4.12, =0.024, number-needed-to-treat [NNT] =7, 95% CI =3, 333, =0.046; valbenazine: RR =3.05, 95% CI =1.81, 5.11, <0.001, NNT =4, 95% CI =3, 6, <0.001). Less consistent results emerged from patient-rated global impression-based response (=0.15) and clinical global impression for deutetrabenazine (=0.088), and for clinical global impression change for valbenazine (=0.67). In an open-label extension (OLE) study of deutetrabenazine (≤54 weeks) and a dose-blinded valbenazine study (≤48 weeks), responder rates increased over time. With valbenazine, discontinuation effects were studied, showing TD symptom recurrence towards baseline severity levels within 4 weeks after valbenazine withdrawal. No increased cumulative or specific adverse (AEs) events versus placebo (acute trials) in extension versus acute trial data were observed.
CONCLUSION
The 2 VMAT-2 inhibitors, valbenazine and deutetrabenazine, are effective in treating TD, both acutely and long-term, without concerns about increased risk of depression or suicide in the TD population. No head-to-head comparison among VMAT-2 inhibitors and no high-quality, meta-analyzable data are available for tetrabenazine in patients with TD.
Topics: Antipsychotic Agents; Humans; Randomized Controlled Trials as Topic; Tardive Dyskinesia; Tetrabenazine; Valine; Vesicular Monoamine Transport Proteins
PubMed: 29795977
DOI: 10.2147/DDDT.S133205 -
Neurobiology of Disease Feb 2021Neurodegenerative disorders such as Alzheimer's disease (AD), Lewy body diseases (LBD), and the amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD)... (Meta-Analysis)
Meta-Analysis
Neurodegenerative disorders such as Alzheimer's disease (AD), Lewy body diseases (LBD), and the amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD) spectrum are defined by the accumulation of specific misfolded protein aggregates. However, the mechanisms by which each proteinopathy leads to neurodegeneration remain elusive. We hypothesized that there is a common "pan-neurodegenerative" gene expression signature driving pathophysiology across these clinically and pathologically diverse proteinopathies. To test this hypothesis, we performed a systematic review of human CNS transcriptomics datasets from AD, LBD, and ALS-FTD patients and age-matched controls in the Gene Expression Omnibus (GEO) and ArrayExpress databases, followed by consistent processing of each dataset, meta-analysis, pathway enrichment, and overlap analyses. After applying pre-specified eligibility criteria and stringent data pre-processing, a total of 2600 samples from 26 AD, 21 LBD, and 13 ALS-FTD datasets were included in the meta-analysis. The pan-neurodegenerative gene signature is characterized by an upregulation of innate immunity, cytoskeleton, and transcription and RNA processing genes, and a downregulation of the mitochondrial electron transport chain. Pathway enrichment analyses also revealed the upregulation of neuroinflammation (including Toll-like receptor, TNF, and NFκB signaling) and phagocytosis, and the downregulation of mitochondrial oxidative phosphorylation, lysosomal acidification, and ubiquitin-proteasome pathways. Our findings suggest that neuroinflammation and a failure in both neuronal energy metabolism and protein degradation systems are consistent features underlying neurodegenerative diseases, despite differences in the extent of neuronal loss and brain regions involved.
Topics: Alzheimer Disease; Amyotrophic Lateral Sclerosis; Brain; Energy Metabolism; Frontotemporal Dementia; Humans; Inflammation; Inflammation Mediators; Lewy Body Disease; Neurodegenerative Diseases; Proteostasis; Transcriptome
PubMed: 33347974
DOI: 10.1016/j.nbd.2020.105225 -
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 -
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 Journal of Clinical... Feb 2024Calprotectin is a calcium-binding-S100-protein synthetized mainly in neutrophils which has been demonstrated to be an accurate biomarker of the presence of these cells.... (Review)
Review
BACKGROUND
Calprotectin is a calcium-binding-S100-protein synthetized mainly in neutrophils which has been demonstrated to be an accurate biomarker of the presence of these cells. Gut barrier dysfunction in patients with advanced chronic liver disease (ACLD), in addition to the lack of noninvasive tools for diagnosis and prognosis of cirrhosis decompensations, has raised interest in this biomarker.
AIMS
Our aim is to summarize the current evidence regarding the role of calprotectin in terms of its diagnostic and prognostic utility in ACLD.
METHODS
We performed a systematic search (PROSPERO registration no. CRD42023389069) of original articles published without any restrictions on the publication date until January 2023 providing information about calprotectin for the prognosis or diagnosis of ACLD and its decompensations in adult patients.
RESULTS
A total 227 articles were identified, and 26 observational studies finally met the inclusion criteria. In 14 studies, calprotectin was measured in ascitic fluid, all of which reported higher calprotectin values in spontaneous bacterial peritonitis, while cut-off points for its diagnosis were proposed in nine studies. Three studies reported higher faecal calprotectin levels in patients with hepatic encephalopathy and portal hypertension. Four studies evaluated faecal calprotectin and one plasma calprotectin as biomarkers for gut barrier integrity and bacterial translocation.
CONCLUSIONS
Calprotectin is emerging as a promising biomarker in ACLD, particularly for the management of bacterial infections and alcohol-related liver disease. Further research with better study designs should help to determine the feasibility of calprotectin measurement in routine clinical practice.
Topics: Adult; Humans; Biomarkers; Hypertension, Portal; Leukocyte L1 Antigen Complex; Liver Cirrhosis; Prognosis
PubMed: 37849372
DOI: 10.1111/eci.14111 -
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