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Molecular Psychiatry Jul 2016The adult form of attention-deficit/hyperactivity disorder has a prevalence of up to 5% and is the most severe long-term outcome of this common disorder. Family studies... (Meta-Analysis)
Meta-Analysis Review
The adult form of attention-deficit/hyperactivity disorder has a prevalence of up to 5% and is the most severe long-term outcome of this common disorder. Family studies in clinical samples as well as twin studies suggest a familial liability and consequently different genes were investigated in association studies. Pharmacotherapy with methylphenidate (MPH) seems to be the first-line treatment of choice in adults with attention-deficit hyperactive disorder (ADHD) and some studies were conducted on the genes influencing the response to this drug. Finally some peripheral biomarkers were identified in ADHD adult patients. We believe this work is the first systematic review and meta-analysis of candidate gene association studies, pharmacogenetic and biochemical (metabolomics) studies performed in adults with ADHD to identify potential genetic, predictive and peripheral markers linked specifically to ADHD in adults. After screening 5129 records, we selected 87 studies of which 61 were available for candidate gene association studies, 5 for pharmacogenetics and 21 for biochemical studies. Of these, 15 genetic, 2 pharmacogenetic and 6 biochemical studies were included in the meta-analyses. We obtained an association between adult ADHD and the gene BAIAP2 (brain-specific angiogenesis inhibitor 1-associated protein 2), even after Bonferroni correction, with any heterogeneity in effect size and no publication bias. If we did not apply the Bonferroni correction, a trend was found for the carriers allele 9R of dopamine transporter SLC6A3 40 bp variable tandem repeat polymorphism (VNTR) and for 6/6 homozygotes of SLC6A3 30 bp VNTR. Negative results were obtained for the 9-6 haplotype, the dopamine receptor DRD4 48 bp VNTR, and the enzyme COMT SNP rs4680. Concerning pharmacogenetic studies, no association was found for the SLC6A3 40 bp and response to MPH with only two studies selected. For the metabolomics studies, no differences between ADHD adults and controls were found for salivary cortisol, whereas lower serum docosahexaenoic acid (DHA) levels were found in ADHD adults. This last association was significant even after Bonferroni correction and in absence of heterogeneity. Other polyunsaturated fatty acids (PUFAs) such as AA (arachidonic acid), EPA (eicosapentaenoic acid) and DyLA (dihomogammalinolenic acid) levels were not different between patients and controls. No publication biases were observed for these markers. Genes linked to dopaminergic, serotoninergic and noradrenergic signaling, metabolism (DBH, TPH1, TPH2, DDC, MAOA, MAOB, BCHE and TH), neurodevelopment (BDNF and others), the SNARE system and other forty genes/proteins related to different pathways were not meta-analyzed due to insufficient data. In conclusion, we found that there were not enough genetic, pharmacogenetic and biochemical studies of ADHD in adults and that more investigations are needed. Moreover we confirmed a significant role of BAIAP2 and DHA in the etiology of ADHD exclusively in adults. Future research should be focused on the replication of these findings and to assess their specificity for ADHD.
Topics: Adult; Alleles; Attention Deficit Disorder with Hyperactivity; Biomarkers; Docosahexaenoic Acids; Dopamine Plasma Membrane Transport Proteins; Female; Gene Frequency; Genetic Association Studies; Genotype; Humans; Male; Methylphenidate; Minisatellite Repeats; Nerve Tissue Proteins; Pharmacogenetics; Polymorphism, Genetic; Receptors, Dopamine D4
PubMed: 27217152
DOI: 10.1038/mp.2016.74 -
Nutrients Sep 2021The primary aim was to systematically review the current evidence investigating if dietary interventions rich in protein lead to improved body weight management in... (Meta-Analysis)
Meta-Analysis
Are Dietary Proteins the Key to Successful Body Weight Management? A Systematic Review and Meta-Analysis of Studies Assessing Body Weight Outcomes after Interventions with Increased Dietary Protein.
The primary aim was to systematically review the current evidence investigating if dietary interventions rich in protein lead to improved body weight management in adults with excessive body weight. The secondary aim was to investigate potential modifying effects of phenotyping. A systematic literature search in PubMed, Web of Science, and Cochrane Library identified 375 randomized controlled trials with 43 unique trials meeting the inclusion criteria. The Cochrane collaboration tool was used for a thorough risk of bias assessment. Based on 37 studies evaluating effects of dietary protein on body weight, the participants with increased protein intake (ranging from 18-59 energy percentage [E%]) were found to reduce body weight by 1.6 (1.2; 2.0) kg (mean [95% confidence interval]) compared to controls (isocaloric interventions with energy reduction introduced in certain studies). Individuals with prediabetes were found to benefit more from a diet high in protein compared to individuals with normoglycemia, as did individuals without the obesity risk allele (AA genotype) compared to individuals with the obesity risk alleles (AG and GG genotypes). Thus, diets rich in protein would seem to have a moderate beneficial effect on body weight management.
Topics: Adult; Body Mass Index; Body Weight; Diet, High-Protein; Dietary Proteins; Exercise; Female; Humans; Male; Middle Aged; Obesity; Overweight; Randomized Controlled Trials as Topic; Weight Gain; Weight Loss; Young Adult
PubMed: 34579069
DOI: 10.3390/nu13093193 -
Jornal Brasileiro de Pneumologia :... 2024To evaluate the effect of treatment with the combination of three cystic fibrosis transmembrane conductance regulator (CFTR) modulators-elexacaftor+tezacaftor+ivacaftor... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the effect of treatment with the combination of three cystic fibrosis transmembrane conductance regulator (CFTR) modulators-elexacaftor+tezacaftor+ivacaftor (ETI)-on important clinical endpoints in individuals with cystic fibrosis.
METHODS
This was a systematic review and meta-analysis of randomized clinical trials that compared the use of ETI in individuals with CF and at least one F508del allele with that of placebo or with an active comparator such as other combinations of CFTR modulators, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations and the Patients of interest, Intervention to be studied, Comparison of interventions, and Outcome of interest (PICO) methodology. We searched the following databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from their inception to December 26th, 2022. The risk of bias was assessed using the Cochrane risk-of-bias tool, and the quality of evidence was based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE).
RESULTS
We retrieved 54 studies in the primary search. Of these, 6 met the inclusion criteria and were analyzed (1,127 patients; 577 and 550 in the intervention and control groups, respectively). The meta-analysis revealed that the use of ETI increased FEV1% [risk difference (RD), +10.47%; 95% CI, 6.88-14.06], reduced the number of acute pulmonary exacerbations (RD, -0.16; 95% CI, -0.28 to -0.04), and improved quality of life (RD, +14.93; 95% CI, 9.98-19.89) and BMI (RD, +1.07 kg/m2; 95% CI, 0.90-1.25). Adverse events did not differ between groups (RD, -0.03; 95% CI, -0.08 to 0.01), and none of the studies reported deaths.
CONCLUSIONS
Our findings demonstrate that ETI treatment substantially improves clinically significant, patient-centered outcomes.
Topics: Humans; Alleles; Cystic Fibrosis Transmembrane Conductance Regulator; Cystic Fibrosis; Quality of Life; Pyridines; Indoles; Pyrazoles; Aminophenols; Quinolones; Pyrrolidines; Benzodioxoles
PubMed: 38198345
DOI: 10.36416/1806-3756/e20230187 -
Children (Basel, Switzerland) Jan 2023: Some variants in () and () genes can be associated with oral diseases. Herein, we designed a systematic review and meta-analysis to evaluate the association of (, ,... (Review)
Review
Evaluation of Beta-Defensin 1 and Mannose-Binding Lectin 2 Polymorphisms in Children with Dental Caries Compared to Caries-Free Controls: A Systematic Review and Meta-Analysis.
: Some variants in () and () genes can be associated with oral diseases. Herein, we designed a systematic review and meta-analysis to evaluate the association of (, , and ) and ( and ) polymorphisms with the susceptibility to dental caries (DC) in children. : A systematic literature search was conducted in the PubMed/Medline, Web of Science, Scopus, and Cochrane Library databases until 3 December 2022, without any restrictions. The odds ratio (OR), along with a 95% confidence interval (CI) of the effect sizes, are reported. Analyses including a subgroup analysis, a sensitivity analysis, and funnel plot analyses were conducted. : A total of 416 records were identified among the databases, and nine articles were entered into the meta-analysis. A significant relationship was found between the T allele of polymorphism and DC susceptibility, and the T allele was related to an elevated risk of DC in children (OR = 1.225; 95%CI: 1.022, 1.469; = 0.028; I = 0%). No other polymorphisms were associated with DC. All articles were of moderate quality. Egger's test in homozygous and dominant models demonstrated a significant publication bias for the association of polymorphism with DC risk. : The results demonstrated that the T allele of polymorphism had an elevated risk for DC in children. However, there were only few studies that evaluated this association.
PubMed: 36832361
DOI: 10.3390/children10020232 -
Cureus Jun 2023Bullous pemphigoid (BP) is an autoimmune blistering disease that mainly affects the elderly. The human leukocyte antigen (HLA) system is believed to be one of the... (Review)
Review
Bullous pemphigoid (BP) is an autoimmune blistering disease that mainly affects the elderly. The human leukocyte antigen (HLA) system is believed to be one of the genetic factors involved in the development of BP. The connection between major histocompatibility complex class II, specifically HLA-DQA1, and BP remains inconclusive. The objective of this review is to find potential associations between BP and HLA-DQA1 alleles, identify the HLA-DQA1 alleles associated with an increased or decreased risk of developing BP, and highlight literature gaps for future research. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were used to conduct a literature review. Databases used included PubMed/MEDLINE, Google Scholar, Embase, and Cochrane Library. Only studies written in English and conducted after 2000 that investigated the association between HLA-DQA1 and BP in human subjects were included. Odds ratios were calculated from the data provided in the studies, and a meta-analysis was conducted using Review Manager (The Cochrane Collaboration, London, United Kingdom) and MetaXL (EpiGear International Pty Ltd., Queensland, Australia) software. The systematic review found five eligible studies, and all were included in the meta-analysis. Results show an increased odds for BP in the HLA-DQA1*05:05 loci (odds ratio (OR) = 2.25; 95% confidence interval (CI) = 1.80, 2.80) and decreased odds for BP in the HLA-DQA1*02:01 loci (OR = 0.50; 95% CI = 0.36, 0.70). Further research is needed to confirm these findings and explore the potential clinical implications for personalized medicine approaches in BP patients.
PubMed: 37416040
DOI: 10.7759/cureus.39923 -
BMC Medical Genetics Sep 2011Despite some studies suggesting a possible association between human leukocyte antigen, HLA-B*5801 and allopurinol induced Stevens-Johnson Syndrome (SJS) and Toxic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Despite some studies suggesting a possible association between human leukocyte antigen, HLA-B*5801 and allopurinol induced Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), the evidence of association and its magnitude remain inconclusive. This study aims to systematically review and meta-analyze the association between HLA-B*5801 allele and allopurinol-induced SJS/TEN.
METHODS
A comprehensive search was performed in databases including MEDLINE, Pre-MEDLINE, Cochrane Library, EMBASE, International Pharmaceutical Abstracts (IPA), CINAHL, PsychInfo, the WHO International, Clinical Trial Registry, and ClinicalTrial.gov from their inceptions to June 2011. Only studies investigating association between HLA-B*5801 with allopurinol-induced SJS/TEN were included. All studies were extracted by two independent authors. The primary analysis was the carrier frequency of HLA-B*5801 comparison between allopurinol-induced SJS/TEN cases and each comparative group. The pooled odds ratios were calculated using a random effect model.
RESULTS
A total of 4 studies with 55 SJS/TEN cases and 678 matched-controls (allopurinol-tolerant control) was identified, while 5 studies with 69 SJS/TEN cases and 3378 population-controls (general population) were found. SJS/TEN cases were found to be significantly associated with HLA-B*5801 allele in both groups of studies with matched-control (OR 96.60, 95%CI 24.49-381.00, p < 0.001) and population-control (OR 79.28, 95%CI 41.51-151.35, p < 0.001). Subgroup analysis for Asian and Non-Asian population yielded similar findings.
CONCLUSION
We found a strong and significant association between HLA-B*5801 and allopurinol-induced SJS/TEN. Therefore, HLA-B*5801 allele screening may be considered in patients who will be treated with allopurinol.
Topics: Adult; Aged; Aged, 80 and over; Alleles; Allopurinol; Case-Control Studies; Female; Genotype; HLA-B Antigens; Heterozygote; Humans; Male; Middle Aged; Odds Ratio; Stevens-Johnson Syndrome
PubMed: 21906289
DOI: 10.1186/1471-2350-12-118 -
Frontiers in Endocrinology 2022The relationships between the rs1801282 and rs3856806 polymorphisms in nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) gene and obesity... (Meta-Analysis)
Meta-Analysis
G Allele of the rs1801282 Polymorphism in PPARγ Gene Confers an Increased Risk of Obesity and Hypercholesterolemia, While T Allele of the rs3856806 Polymorphism Displays a Protective Role Against Dyslipidemia: A Systematic Review and Meta-Analysis.
BACKGROUND
The relationships between the rs1801282 and rs3856806 polymorphisms in nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) gene and obesity indexes as well as serum lipid levels have been extensively investigated in various studies, but the results were inconsistent and even contradictory.
METHODS
PubMed, Google Scholar, Embase, Cochrane Library, Web of Science, Wanfang, CNKI and VIP databases were searched for eligible studies. The random-effTPDEects model was used, and standardized mean difference (SMD) with 95% confidence interval (CI) was calculated to estimate the differences in obesity indexes and serum lipid levels between the subjects with different genotypes in a dominant model. Heterogeneity among studies was assessed by Cochran's x-based Q-statistic test. Publication bias was identified by using Begg's test.
RESULTS
One hundred and twenty studies (70,317 subjects) and 33 studies (18,353 subjects) were identified in the analyses for the rs1801282 and rs3856806 polymorphisms, respectively. The G allele carriers of the rs1801282 polymorphism had higher levels of body mass index (SMD = 0.08 kg/m, 95% CI = 0.04 to 0.12 kg/m, < 0.001), waist circumference (SMD = 0.12 cm, 95% CI = 0.06 to 0.18 cm, < 0.001) and total cholesterol (SMD = 0.07 mmol/L, 95% CI = 0.02 to 0.11 mmol/L, < 0.01) than the CC homozygotes. The T allele carriers of the rs3856806 polymorphism had lower levels of low-density lipoprotein cholesterol (SMD = -0.09 mmol/L, 95% CI = -0.15 to -0.03 mmol/L, < 0.01) and higher levels of high-density lipoprotein cholesterol (SMD = 0.06 mmol/L, 95% CI = 0.02 to 0.10 mmol/L, < 0.01) than the CC homozygotes.
CONCLUSIONS
The meta-analysis suggests that the G allele of the rs1801282 polymorphism confers an increased risk of obesity and hypercholesterolemia, while the T allele of the rs3856806 polymorphism displays a protective role against dyslipidemia, which can partly explain the associations between these polymorphisms and cardiovascular disease.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier [CRD42022319347].
Topics: Alleles; Cholesterol, HDL; Dyslipidemias; Humans; Hypercholesterolemia; Obesity; PPAR gamma; Polymorphism, Single Nucleotide
PubMed: 35846293
DOI: 10.3389/fendo.2022.919087 -
Genetics and Molecular Research : GMR May 2013Genetic variations in the caspase genes CASP-3 and CASP-7 are known to be involved in apoptosis, cytokine maturation, cell growth and differentiation. Polymorphisms of... (Meta-Analysis)
Meta-Analysis Review
Genetic variations in the caspase genes CASP-3 and CASP-7 are known to be involved in apoptosis, cytokine maturation, cell growth and differentiation. Polymorphisms of CASP-3 and CASP-7 genes have been increasingly recognized as important regulators in the development of cancer. However, whether there is a specific association is still controversial. Therefore, we made a Human Genome Epidemiology review and meta-analysis to explore the association between polymorphisms of CASP-3 and CASP-7 genes and cancer risk. Based on the inclusion criteria, we examined 9 case-control studies, with a total of 3142 cancer cases and 3670 healthy controls. Meta-analysis results showed that the homozygote (CC) of rs2705897 in the CASP-3 gene is positively associated with cancer susceptibility [odds ratio (OR) = 4.36, 95% confidence interval (CI) = 1.26-15.11, P = 0.02], while the C allele and C carrier (TC+CC) of rs1049216 are negatively associated with cancer risk (OR = 0.81, 95%CI = 0.69-0.95, P = 0.01; OR = 0.78, 95%CI = 0.63-0.97, P = 0.02, respectively). The G allele and G carrier of rs4647603 (A/G) in CASP-3 had positive associations with cancer susceptibility (OR = 1.69, 95%CI = 1.37-2.09, P < 0.001; OR = 1.93, 95%CI = 1.26-2.93, P = 0.002, respectively). The T allele of rs12415607, the G allele and homozygote (GG) of rs2227310, and homozygote (CC) of rs3124740 also had positive associations with cancer risk (OR = 1.18, 95%CI = 1.02-1.37, P = 0.03; OR = 1.17, 95%CI = 1.01-1.34, P = 0.03; OR = 1.34, 95%CI = 1.04-1.74, P = 0.03; OR = 1.30, 95%CI = 1.04-1.63, P = 0.02, respectively). In addition, homozygote (AA) of rs11196418 showed a significant negative association with cancer risk (OR = 0.36, 95%CI = 0.14-0.93, P = 0.03). These meta-analysis results demonstrated that CASP-3 and CASP-7 genetic polymorphisms are involved in the pathogenesis of cancer.
Topics: Caspase 3; Caspase 7; Genetic Association Studies; Genetic Predisposition to Disease; Genome, Human; Humans; Neoplasms; Polymorphism, Single Nucleotide; Publication Bias; Risk Factors
PubMed: 23765963
DOI: 10.4238/2013.May.13.10 -
Gastroenterology Research and Practice 2019Functional dyspepsia (FD) is a common chronic gastrointestinal disorder with a complex, undefined mechanism. Clustering of patients with FD in families highlights the... (Review)
Review
Functional dyspepsia (FD) is a common chronic gastrointestinal disorder with a complex, undefined mechanism. Clustering of patients with FD in families highlights the role of genetic factors in the pathogenesis of FD. We performed a systematic review and meta-analysis to clarify the associations between specific gene polymorphisms and FD susceptibility. PubMed, EMBASE, the Cochrane Library, and HuGE database were searched. An additive model was adopted to determine whether previous studied genes are associated with FD susceptibility. Carriers of minor allele in GNB3 825C>T (OR = 1.15, 95% CI 0.99-1.34, = 0.07), SCL6A4 5HTTLPR (OR = 0.92, 95% CI 0.75-1.12, = 0.40), and CCK-1R 779T>C (OR = 0.86, 95% CI 0.72-1.03, = 0.09) genes failed to demonstrate susceptibility to FD. In a subgroup analysis, only minor allele (T) in GNB3 825C>T was associated with an increased susceptibility to the epigastric pain syndrome subtype (OR = 1.34, 95% CI 1.10-1.63, = 0.003). Our meta-analysis based on available studies using an additive model failed to show that GNB3, SCL6A4, and CCK-1R polymorphisms are associated with FD susceptibility.
PubMed: 31178907
DOI: 10.1155/2019/3420548 -
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