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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 -
Gene Dec 2023Autism spectrum disorder (ASD) is neurodevelopmental disorder characterized by stereotyped behavior and deficits in communication and social interactions. To date,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Autism spectrum disorder (ASD) is neurodevelopmental disorder characterized by stereotyped behavior and deficits in communication and social interactions. To date, numerous studies have investigated the associations between genetic variants and ASD risk. However, the results of these published studies lack a clear consensus. In the present study, we performed a systematic review on the association between genetic variants and ASD risk. Meanwhile, we conducted a meta-analysis on available data to identify the association between the single nucleotide polymorphisms (SNPs) of candidate genes and ASD risk.
METHODS
We systematically searched public databases including English and Chinese from their inception to August 1, 2022. Two independent reviewers extracted data and assessed study quality. Odds ratio and 95 % confidence interval were used as effect indexes to evaluate the association between the SNPs of candidate genes and the risk of ASD. Heterogeneity was explored through subgroup, sensitivity, and meta-regression analyses. Publication bias was assessed by using Egger's and Begg's tests for funnel plot asymmetry. In addition, TSA analysis were performed to confirm the study findings.
RESULTS
We summarized 84 SNPs of 32 candidate genes from 81 articles included in the study. Subsequently, we analyzed 16 SNPs of eight genes by calculating pooled ORs, and identified eight significant SNPs of contactin associated protein 2 (CNTNAP2), methylentetrahydrofolate reductase (MTHFR), oxytocin receptor (OXTR), and vitamin D receptor (VDR). Results showed that seven SNPs, including the CNTNAP2 rs2710102 (homozygote, heterozygote, dominant and allelic models) and rs7794745 (heterozygote and dominant models), MTHFR C677T (homozygote, heterozygote, dominant, recessive and allelic models) and A1298C (dominant and allelic models), OXTR rs2254298 (homozygote and recessive models), VDR rs731236 (homozygote, dominant, recessive and allelic models) and rs2228570 (homozygote and recessive models), were showed to be correlated with an increased ASD risk. By contrast, the VDR rs7975232 was correlated with a decreased the risk of ASD under the homozygote and allelic models.
CONCLUSION
Our study summarized research evidence on the genetic variants of ASD and provides a broad and detailed overview of ASD risk genes. The C677T and A1298C polymorphisms of MTHFR, rs2710102 and rs7794745 polymorphisms of CNTNAP2, rs2254298 polymorphism of OXTR, and rs731236 and rs2228570 polymorphisms of VDR were genetic risk factors. The rs7975232 polymorphism of VDR was a genetic protective factor for ASD. Our study provides novel clues to clinicians and healthcare decision-makers to predict ASD susceptibility.
Topics: Humans; Autism Spectrum Disorder; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Alleles; Heterozygote; Methylenetetrahydrofolate Reductase (NADPH2)
PubMed: 37598788
DOI: 10.1016/j.gene.2023.147723 -
Tumour Biology : the Journal of the... May 2014The vitamin D receptor (VDR) can influence cancer susceptibility through binding to vitamin D. However, the previous studies were contradictory. Therefore this... (Meta-Analysis)
Meta-Analysis Review
The vitamin D receptor (VDR) can influence cancer susceptibility through binding to vitamin D. However, the previous studies were contradictory. Therefore this meta-analysis was conducted to clarify the association between VDR polymorphisms (BsmI, TaqI, FokI, and ApaI) and cancer risk. One hundred twenty-six studies were enrolled through PubMed. For VDR BsmI polymorphism, significantly increased cancer risks were observed in the overall analysis. In the further stratified analysis, increased risks were observed in colorectal and skin cancer, especially in Caucasian population. However, no significant associations were observed in other VDR polymorphisms in the overall analysis. In the further subgroup analysis, increased risks were found in oral, breast, and basal cell cancer while decreased risk was found in prostate cancer in t allele carriers of TaqI polymorphism. For VDR FokI polymorphism, increased risks were found in ovarian and skin cancer while decreased risk in glioma in f allele carriers. For VDR ApaI polymorphism, increased risk was observed in basal cell cancer, especially in Asian population in a allele carriers. In conclusion, these results indicated that b allele of BamI polymorphism was a risk factor for cancer susceptibility. Meanwhile, t allele of TaqI polymorphism was a risk factor for oral, breast, and basal cell cancer and a protective factor for prostate cancer. Moreover, f allele of FokI polymorphism was a risk factor for ovarian and skin cancer and a protective factor for glioma. Finally, a allele of ApaI polymorphism was a risk factor for basal cell cancer in Asian population.
Topics: Alleles; Deoxyribonucleases, Type II Site-Specific; Genetic Predisposition to Disease; Humans; Neoplasms; Polymorphism, Genetic; Publication Bias; Receptors, Calcitriol; Risk
PubMed: 24408013
DOI: 10.1007/s13277-013-1544-y -
International Journal of Stroke :... Feb 2013Paraoxonase is known to play an important role in the pathophysiology of atherosclerosis. Genetic variants of the paraoxonase gene have been implicated as risk factors... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Paraoxonase is known to play an important role in the pathophysiology of atherosclerosis. Genetic variants of the paraoxonase gene have been implicated as risk factors for atherosclerotic diseases such as coronary artery disease, but individual genetic association studies examining the relationship between the paraoxonase gene polymorphisms and ischaemic stroke have yielded inconsistent results.
AIM
This study aimed to evaluate the association between the paraoxonase gene variants and ischaemic stroke using systematic review with meta-analysis.
METHODS
Relevant studies were identified by searching English and Chinese databases extensively. Allele and genotype frequencies for each included study were extracted. The odds ratio was calculated using a random-effects or fixed-effects model. A Q statistic was used to evaluate homogeneity, and Egger's test and funnel plot were used to assess publication bias.
RESULTS
A total of 28 studies were included and identified for the current meta-analysis. It was found that the R allele or RR genotype of paraoxonase 1 Q192R polymorphism had an increased risk for ischaemic stroke in the general population (192R allele: odds ratio: 1·21, 95% confidence interval: 1·08-1·35, P = 0·0009 and 192RR genotype: odds ratio: 1·25, 95% confidence interval: 1·06-1·49, P = 0·009 in general population, respectively), but there was no significant association between other genetic variants of paraoxonase gene and ischaemic stroke.
CONCLUSIONS
Existing evidence indicates that the Q192R polymorphism (the R allele and RR genotype) is associated with an increased risk of ischaemic stroke in the general population. Future studies with larger sample sizes will be necessary to confirm the present results.
Topics: Alleles; Aryldialkylphosphatase; Brain Ischemia; Genetic Predisposition to Disease; Genotype; Humans; Polymorphism, Genetic; Stroke
PubMed: 22631428
DOI: 10.1111/j.1747-4949.2012.00813.x -
Journal of Affective Disorders Oct 2014Genetic factors may encourage or even cause the occurrence of mood disorders such as anxiety and/or depression. However, despite the significant amount of work and... (Review)
Review
BACKGROUND
Genetic factors may encourage or even cause the occurrence of mood disorders such as anxiety and/or depression. However, despite the significant amount of work and sophisticated technology is not fully elucidated which genes or regions of nuclear or mitochondrial DNA, or which types of genetic changes, alone or in combination, can represent reliable genetic markers of anxiety and/or depression.
OBJECTIVE
To identify whether there are genetic changes that can cause depression or anxiety and if there are genetic markers that can be used to detect these changes.
METHODS
A systematic review of 01.01.2004 to 03.28.2014 was held by VHL (Virtual Health Library). The search was performed with the descriptors ׳׳anxiety׳׳, ׳׳depression׳׳, "mutation" and "genetic markers׳׳. The selected articles were indexed in MEDLINE. The information pertinent to the study was selected, categorized and analyzed. Of the 374 articles found, 29 met the eligibility criteria.
RESULTS
FMR1 gene polymorphisms, dopaminergic (DAT, DRD, COMT), serotonin (5-HTTLPR, HTR1A, HTR2A), interleukins, MCR1, HCN (potassium channel), neurorregulinas, GABAergic (GABA, GAD, DBI) DBI, GABA (Gabra) receptors and GAD genes (GAD1, GAD2) appear to contribute to generate condition of depression or anxiety like. Mutations in mitochondrial DNA in 124pb allele of D2S2944 in ofil 1 and 2 loci of chromosomes 4 and 7, respectively, and the chromosomes 8p, 17p and 15q appear to be associated with the origin of depression or anxiety.
CONCLUSION
Some studies show only associations with one of the disorders, mainly anxiety. Few have shown association with both simultaneously. Other studies showed specific association of gender, or even specific ethnic groups. It was noticed, controversies over certain markers. Interesting results were observed in combination of changes, especially in cases of SNPs, indicating that perhaps this is the most appropriate way to find reliable markers.
Topics: Alleles; Anxiety; Anxiety Disorders; Depression; Depressive Disorder; Genetic Markers; Genetic Predisposition to Disease; Humans; Mutation; Polymorphism, Genetic; Polymorphism, Single Nucleotide
PubMed: 25106036
DOI: 10.1016/j.jad.2014.07.016 -
International Ophthalmology Jan 2022Diabetic retinopathy (DR) is a medical condition caused by damage to the blood vessels of retina tissue due to diabetes mellitus. DR leads to injury in neural and... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Diabetic retinopathy (DR) is a medical condition caused by damage to the blood vessels of retina tissue due to diabetes mellitus. DR leads to injury in neural and vascular structures and is reported to be significantly influenced by inflammation and inflammatory mediators like cytokines. In this study, a systematic review and meta-analysis were performed to analyze the association between cytokine gene polymorphisms and DR.
METHODS
We identified relevant studies from Scopus, PubMed, and Google scholar databases. Allele and genotype frequencies were pooled. Heterogeneity and publication bias were explored. The odds ratio (OR) and corresponding 95% confidence intervals (CIs) were calculated to estimate the relation.
RESULTS
A total of 3337 cases and 4945 controls in 19 eligible studies were included in the meta-analysis. Overall, results indicated the negative association between the cytokine gene polymorphisms and DR susceptibility in the allelic model (IFN-γ (rs2430561): OR 0.64, [CI]: 0.5 to 0.82; and TGF-β (rs1800471): [OR] = 0.15, [CI]: 0.03 to 0.79); and also, in the dominant model (IFN-γ (rs2430561): OR = 0.4, [CI]: 0.22 to 0.75; and TGF-β (rs1800471): OR = 0.14, [CI]: 0.05 to 0.4).
CONCLUSION
The present study suggests that IFN-γ (rs2430561) and TGF-β (rs1800471) polymorphisms are associated with decreased susceptibility to DR.
Topics: Cytokines; Diabetes Mellitus; Diabetic Retinopathy; Genetic Predisposition to Disease; Genotype; Humans; Polymorphism, Genetic; Polymorphism, Single Nucleotide
PubMed: 34432176
DOI: 10.1007/s10792-021-02011-9 -
Psychiatric Genetics Apr 2016The role of apolipoprotein E (APOE) in Alzheimer's disease and other dementias has been investigated intensively. However, the relationship between APOE and delirium has... (Meta-Analysis)
Meta-Analysis Review
The role of apolipoprotein E (APOE) in Alzheimer's disease and other dementias has been investigated intensively. However, the relationship between APOE and delirium has only recently been explored in studies that have included relatively small samples. A meta-analysis of the published pooled data is timely to explore the relationship between APOE and delirium and to inform further research in this topic. PubMed, EBSCOhost, Google Scholar, Scopus, all EBM Reviews (OVID) and the Cochrane Database of Systematic Reviews were searched with relevant keywords and from the references of relevant papers. Ten papers were found that examined the relationship between APOE and delirium. Data were extracted from eight of them and pooled for meta-analysis using random effects with R software. Data from 1762 participants, of whom 479 (27.2%) were diagnosed with delirium, showed low heterogeneity (Q=13.11, d.f.=7, P=0.07; I=44.86%). The possession of the APOE ε4 allele has a small (log odds ratio: 0.18, 95% confidence interval: 0.23-0.59), nonsignificant (P=0.38) effect on the presence of delirium. No publication bias was identified. The metapower of the pooled data was low (α=0.05, power=0.65). On analysing the studies to date, it seems that there is no association between APOE and the occurrence of delirium. We suggest that further studies are needed with greater number of patients to clarify any association as well as to examine for other patterns of association including relevance for subgroups of patients who develop delirium and for effects on the phenotype of delirium and the outcomes.
Topics: Alleles; Alzheimer Disease; Apolipoprotein E4; Delirium; Genotype; Humans; Odds Ratio
PubMed: 26901792
DOI: 10.1097/YPG.0000000000000122 -
Pediatric Research Oct 2016Two polymorphisms in the murine double minute 2 (MDM2) gene (rs1690916 and rs2279744) have been associated with the risk of osteosarcoma (OS). When we analyzed these two... (Meta-Analysis)
Meta-Analysis Review
Two polymorphisms in the murine double minute 2 (MDM2) gene (rs1690916 and rs2279744) have been associated with the risk of osteosarcoma (OS). When we analyzed these two polymorphisms in two new independents cohorts (Spanish and Slovenian), we found no association. In order to clarify this, we conducted a meta-analysis including six populations, with a total of 246 OS patients and 1,760 controls for rs1690916; and 433 OS patients and 1,959 controls for rs2279744. Pooled odds ratio risks and corresponding 95% CI were estimated to assess the possible associations. Our results showed that these two polymorphisms were not associated with the susceptibility of OS under any genetic model studied. In conclusion, the present meta-analysis indicates that MDM2 rs1690916 and rs2279744 cannot be considered as genetic risk factors for OS susceptibility in the different populations. Therefore, the influence of these two polymorphisms on the risk of OS may be less important than previously suggested. Future studies are needed to confirm these results.
Topics: 3' Untranslated Regions; Alleles; Cohort Studies; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Multicenter Studies as Topic; Odds Ratio; Osteosarcoma; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Proto-Oncogene Proteins c-mdm2; Risk Factors; Slovenia; Spain
PubMed: 27438225
DOI: 10.1038/pr.2016.120 -
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 -
Infection, Genetics and Evolution :... Sep 2016The CCR5 is a chemokine receptor widely expressed by several immune cells that are engaged in inflammatory responses. Some populations have individuals exhibiting a 32bp... (Meta-Analysis)
Meta-Analysis Review
The CCR5 is a chemokine receptor widely expressed by several immune cells that are engaged in inflammatory responses. Some populations have individuals exhibiting a 32bp deletion in the CCR5 gene (CCR5-delta32) that produces a truncated non-functional protein not expressed on the cell surface. This polymorphism, known to be associated with susceptibility to infectious and inflammatory diseases, such as osteomyelitis, pre-eclampsia, systemic lupus erythematous, juvenile idiopathic arthritis, rheumatoid arthritis and HIV/AIDS, is more commonly found in European populations with average frequency of 10%. However, it is also possible to observe a significant frequency in other world populations, such as the Brazilian one. We performed a systematic review and meta-analysis of CCR5-delta32 genetic association studies in Brazilian populations throughout the country to estimate the frequency of this polymorphism. We also compared CCR5-delta32 frequencies across Brazilian regions. The systematic literature reviewed studies involving delta32 allele in Brazilian populations published from 1995 to 2015. Among the reviewed literature, 25 studies including 30 Brazilian populations distributed between the North, Northeast, South and Southeast regions were included in our meta-analysis. We observed an overall allelic frequency of 4% (95%-CI, 0.03-0.05), that was considered moderate and, notably, higher than some European populations, such as Cyprus (2.8%), Italy (3%) and Greece (2.4%). Regarding the regional frequency comparisons between North-Northeast (N-NE) and South-Southeast (S-SE) regions, we observed an allelic frequency of 3% (95%-CI, 0.02-0.04) and 4% (95%-CI, 0.03-0.05), respectively. The populations from S-SE regions had a slightly higher CCR5-delta32 frequency than N-NE regions (OR=1.41, p=0.002). Although there are several studies about the CCR5-delta32 polymorphism and its effect on the immune response of some infectious diseases, this report is the first meta-analysis study that provides a descriptive study of the distribution of CCR5-delta32 allele in Brazilian population.
Topics: Brazil; Gene Frequency; Genetic Association Studies; Humans; Receptors, CCR5; Risk Factors; White People
PubMed: 27208805
DOI: 10.1016/j.meegid.2016.05.024