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The Cochrane Database of Systematic... Nov 2020Sickle cell disease encompasses a group of genetic disorders characterized by the presence of at least one hemoglobin S (Hb S) allele, and a second...
BACKGROUND
Sickle cell disease encompasses a group of genetic disorders characterized by the presence of at least one hemoglobin S (Hb S) allele, and a second abnormal allele that could allow abnormal haemoglobin polymerisation leading to a symptomatic disorder. Autosomal recessive disorders (such as sickle cell disease) are good candidates for gene therapy because a normal phenotype can be restored in diseased cells with only a single normal copy of the mutant gene. This is an update of a previously published Cochrane Review.
OBJECTIVES
The objectives of this review are: - to determine whether gene therapy can improve survival and prevent symptoms and complications associated with sickle cell disease; - to examine the risks of gene therapy against the potential long-term gain for people with sickle cell disease.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises of references identified from comprehensive electronic database searches and searching relevant journals and abstract books of conference proceedings. We also searched online trial registries, Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 21 September 2020.
SELECTION CRITERIA
All randomised or quasi-randomised clinical trials (including any relevant phase 1, 2 or 3 trials) of gene therapy for all individuals with sickle cell disease, regardless of age or setting.
DATA COLLECTION AND ANALYSIS
No trials of gene therapy for sickle cell disease were found.
MAIN RESULTS
No trials of gene therapy for sickle cell disease were reported.
AUTHORS' CONCLUSIONS
No randomised or quasi-randomised clinical trials of gene therapy for sickle cell disease were reported. Thus, no objective conclusions or recommendations in practice can be made on gene therapy for sickle cell disease. This systematic review has identified the need for well-designed, randomised controlled trials to assess the benefits and risks of gene therapy for sickle cell disease.
Topics: Anemia, Sickle Cell; Genetic Therapy; Humans
PubMed: 33251574
DOI: 10.1002/14651858.CD007652.pub7 -
Zygote (Cambridge, England) Aug 2023Fertilization failure (FF) and zygotic arrest after ICSI have a huge effect on both patients and clinicians, but both problems are usually unexpected and cannot be... (Review)
Review
Fertilization failure (FF) and zygotic arrest after ICSI have a huge effect on both patients and clinicians, but both problems are usually unexpected and cannot be properly diagnosed. Fortunately, in recent years, gene sequencing has allowed the identification of multiple genetic variants underlying failed ICSI outcomes, but the use of this approach is still far from routine in the fertility clinic. In this systematic review, the genetic variants associated with FF, abnormal fertilization and/or zygotic arrest after ICSI are compiled and analyzed. Forty-seven studies were included. Data from 141 patients carrying 121 genetic variants affecting 16 genes were recorded and analyzed. In total, 27 variants in (in 50 men) and 26 variants in (in 24 women) are two of the factors related to oocyte activation failure that could explain a high percentage of male-related and female-related FF. Additional variants identified were reported in , and (in men), and , , , , , , and (in women). Most of these variants are pathogenic or potentially pathogenic (89/121, 72.9%), as demonstrated by experimental and/or approaches. Most individuals carried bi-allelic variants (89/141, 63.1%), but pathogenic variants in heterozygosity have been identified for and . Clinical treatment options for affected individuals, such as chemical-assisted oocyte activation (AOA) or cRNA injection in the oocyte, are still experimental. In conclusion, a genetic study of known pathogenic variants may help in diagnosing recurrent FF and zygotic arrest and guide patient counselling and future research perspectives.
Topics: Male; Female; Animals; Sperm Injections, Intracytoplasmic; Zygote; Oocytes; Fertilization
PubMed: 37212058
DOI: 10.1017/S096719942300014X -
Frontiers in Cardiovascular Medicine 2023Carotid atherosclerotic plaque is an important independent risk factor for stroke. Apolipoprotein E (APOE) influences cholesterol levels and certain isoforms are...
INTRODUCTION
Carotid atherosclerotic plaque is an important independent risk factor for stroke. Apolipoprotein E (APOE) influences cholesterol levels and certain isoforms are associated with increased carotid atherosclerosis, though the exact association between APOE and carotid plaque is uncertain. The study aimed to evaluate the association between APOE and carotid plaque.
METHODS
A systematic review was performed to retrieve all studies which examined the association between carotid plaque and APOE. This study was conducted in accordance with the PRISMA guidelines. Independent readers extracted the relevant data from each study including the type of imaging assessment, plaque definition, frequency of APOE E4 carrier status and type of genotyping. Meta-analyses with an assessment of study heterogeneity and publication bias were performed. Results were presented in a forest plot and summarized using a random-effects model.
RESULTS
After screening 838 studies, 17 studies were included for systematic review. A meta-analysis of 5 published studies showed a significant association between 4 homozygosity and carotid plaque [odds ratio (OR), 1.53; 95% CI, 1.16, 2.02; = .003]. Additionally, there was a significant association between patients possessing at least one 4 allele, heterozygotes or homozygotes, and carotid plaque (OR, 1.25; 95% CI, 1.03, 1.52; = .03). Lastly, there was no association between 4 heterozygosity and carotid plaque (OR, 1.08; 95% CI, 0.93, 1.26; = .30).
CONCLUSION
APOE 4 allele is significantly associated with extracranial carotid atherosclerotic plaque, especially for homozygous individuals.
PubMed: 38034385
DOI: 10.3389/fcvm.2023.1155916 -
Frontiers in Genetics 2020A compound heterozygous () variant is a type of germline variant that occurs when each parent donates one alternate allele and these alleles are located at different... (Review)
Review
A compound heterozygous () variant is a type of germline variant that occurs when each parent donates one alternate allele and these alleles are located at different loci within the same gene. Pathogenic germline variants have been identified for some pediatric cancer types but in most studies, variants are overlooked. Thus, the prevalence of pathogenic variants in most pediatric cancer types is unknown. We identified 26 studies (published between 1999 and 2019) that identified a variant in at least one pediatric cancer patient. These studies encompass 21 cancer types and have collectively identified 25 different genes in which a variant occurred. However, the sequencing methods used and the number of patients and genes evaluated in each study were highly variable across the studies. In addition, methods for assessing pathogenicity of variants varied widely and were often not reported. In this review, we discuss technologies and methods for identifying variants, provide an overview of studies that have identified variants in pediatric cancer patients, provide insights into future directions in the field, and give a summary of publicly available pediatric cancer sequencing data. Although considerable insights have been gained over the last 20 years, much has yet to be learned about the involvement of variants in pediatric cancers. In future studies, larger sample sizes, more pediatric cancer types, and better pathogenicity assessment and filtering methods will be needed to move this field forward.
PubMed: 32508881
DOI: 10.3389/fgene.2020.00493 -
International Journal of Environmental... Nov 2022Risk and loss aversion are phenomena with an important influence on decision-making, especially in economic contexts. At present, it remains unclear whether both are... (Review)
Review
Risk and loss aversion are phenomena with an important influence on decision-making, especially in economic contexts. At present, it remains unclear whether both are related, as well as whether they could have an emotional origin. The objective of this review, following the PRISMA statements, is to find consistencies in the genetic bases of risk and loss aversion with the aim of understanding their nature and shedding light on the above issues. A total of 23 empirical research met the inclusion criteria and were included from PubMed and ScienceDirect. All of them reported genetic measures from human samples and studied risk and loss aversion within an economic framework. The results for risk aversion, although with many limitations, attributed mainly to their heterogeneity and the lack of control in the studies, point to the implication of multiple polymorphisms related to the regulation of the serotonergic and dopaminergic pathways. In general, studies found the highest levels of risk aversion were associated with alleles that are linked to lower (higher) sensitivity or levels of dopamine (serotonin). For loss aversion, the scarcity of results prevents us from drawing clear conclusions, although the limited evidence seems to point in the same direction as for risk aversion. Therefore, it seems that risk aversion could have a stable genetical base which, in turn, is closely linked to emotions, but more research is needed to answer whether this phenomenon is related to loss aversion, as well as if the latter could also have an emotional origin. We also provide recommendations for future studies on genetics and economic behavior.
Topics: Humans; Affect; Emotions; Polymorphism, Genetic; Dopamine; Alleles; Decision Making
PubMed: 36361187
DOI: 10.3390/ijerph192114307 -
Gene May 2024This systematic review and meta-analysis aimed to verify the association between single-nucleotide polymorphisms (SNPs) in vitamin D-related genes and the severity or... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis aimed to verify the association between single-nucleotide polymorphisms (SNPs) in vitamin D-related genes and the severity or mortality of coronavirus disease 19 (COVID-19). We systematically searched PubMed, BVS/Bireme, Scopus, Embase, and Web of Science for relevant studies published until November 24, 2023. Twelve studies were included. Thirty-one SNPs related to four genes were studied (VDR, 13 SNPs; GC, 6 SNPs; DHCR7/NADSYN1, 6 SNPs; CYP2R1, 6 SNPs). Eight SNPs were examined in two or more studies (VDR rs731236, rs2228570, rs1544410, rs7975232, rs739837, rs757343, rs11568820, and rs4516035). Meta-analysis showed a significant association between the VDR rs1544410 Bb + bb genotype and b allele and an increased odds of developing severe/critical COVID-19 (Bb + bb vs. BB = 2 studies, OR = 1.73, 95% confidence interval (CI): 1.16-2.57, P = 0.007, I = 0%; b allele vs. B allele = 2 studies, OR = 1.31, 95% CI: 1.03-1.67; P = 0.03; I = 0%). Regarding the mortality rate, VDR rs731236 TT-genotype, TT + Tt genotype, and T allele; VDR rs1544410 bb-genotype, Bb + bb genotype, and b allele; VDR rs7975232 AA-genotype, AA + Aa genotype, and A allele; and VDR rs2228570 ff-genotype, Ff + ff genotype, and f allele were associated with increased odds of death due to COVID-19. In conclusion, the present study suggests that SNPs rs1544410 may serve as a predictive biomarker for COVID-19 severity and rs731236, rs1544410, rs7975232, and rs2228570 as predictive biomarkers for COVID-19 mortality. More well-designed studies involving a larger number of COVID-19 patients are required to validate and replicate these findings.
Topics: Humans; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease; Receptors, Calcitriol; COVID-19; Genotype; Vitamin D
PubMed: 38316264
DOI: 10.1016/j.gene.2024.148236 -
Pharmacogenomics Dec 2023To evaluate the association between gene polymorphisms and susceptibility of antituberculosis drug-induced hepatotoxicity (ATDH). We searched the PubMed, Cochrane... (Meta-Analysis)
Meta-Analysis Review
To evaluate the association between gene polymorphisms and susceptibility of antituberculosis drug-induced hepatotoxicity (ATDH). We searched the PubMed, Cochrane Library, Embase, Web of Science, Wan Fang and China National Knowledge Infrastructure database from inception to 2022. Nine case-control studies with 1129 cases and 2203 controls were included. Among four SNPs reported in two or more studies, the final results indicated that SNP rs4149014 was significantly associated with decreased ATDH risk (dominant model, odds ratio: 0.73; 95% CI: 0.55-0.97; p = 0.03; allele model, odds ratio: 0.69; 95% CI: 0.55-0.86; p = 0.001), and the trial sequential analysis also confirmed this significant association. gene SNP rs4149014 was significantly associated with lower risk of ATDH susceptibility.
Topics: Humans; Genotype; Genetic Predisposition to Disease; Antitubercular Agents; Polymorphism, Single Nucleotide; Alleles; Chemical and Drug Induced Liver Injury; Liver-Specific Organic Anion Transporter 1
PubMed: 38019119
DOI: 10.2217/pgs-2023-0168 -
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 -
Reviews in Medical Virology Jul 2022Novel coronavirus disease 2019 (COVID-19) poses a global threat, due to its fluctuating frequency and lethality. Published data revealed associations of COVID-19... (Meta-Analysis)
Meta-Analysis Review
Novel coronavirus disease 2019 (COVID-19) poses a global threat, due to its fluctuating frequency and lethality. Published data revealed associations of COVID-19 susceptibility and severity with host genetic polymorphisms in renin-angiotensin-aldosterone system (RAAS)-related genes including angiotensin-converting enzyme (ACE)1, ACE2, and transmembrane protease (TMPRSS)2. However, the findings remain inconclusive. Accordingly, we aimed to clarify associations of genetic variants in those genes with COVID-19 susceptibility and severity using a systematic review with meta-analysis. From inception through 1 July 2021, a literature search was performed using PubMed, Scopus, Web of Science, and Cochrane Library databases. Allelic distributions for each polymorphism were calculated as pooled odds ratios (OR) with 95% confidence intervals (CI) to assess the strength of association. A total of 3333 COVID-19 patients and 5547 controls from 11 eligible studies were included. From a systematic review, ACE1 rs1799752, ACE1 rs4646994, ACE2 rs2285666, and TMPRSS2 rs12329760 were identified as common polymorphisms of RAAS-related genes. Meta-analysis showed a significant association between TMPRSS2 rs12329760 C-allele and an increased risk of developing severe COVID-19 (OR = 1.32, 95% CI: 1.01, 1.73). Likewise, additional meta-analyses uncovered that both ACE1 rs4646994 DD-genotype and ACE2 rs2285666 GG-genotype carriers had a significantly increased risk of developing severe COVID-19 (OR = 2.06, 95% CI: 1.45, 2.93; OR = 2.14, 95% CI: 1.26, 3.66; respectively). Genetic polymorphisms of ACE1 rs4646994 DD-genotype, ACE2 rs2285666 GG-genotype, and TMPRSS2 rs12329760 CC-genotype and C-allele may serve as predictive models of COVID-19 severity.
Topics: Angiotensin-Converting Enzyme 2; COVID-19; Humans; Peptidyl-Dipeptidase A; Polymorphism, Genetic; SARS-CoV-2; Serine Endopeptidases
PubMed: 34997794
DOI: 10.1002/rmv.2323 -
BMC Medical Genomics Apr 2021Multiple factors have been attributed to acne vulgaris predisposition and individual variations in the severity of skin symptoms, and genetics stood out as one of the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Multiple factors have been attributed to acne vulgaris predisposition and individual variations in the severity of skin symptoms, and genetics stood out as one of the major factors.
METHODS
We performed a systematic review on the genes and their variants that have been investigated for association with acne presentation and severity. A random-effect meta-analysis using the allele model (minor allele vs. major allele) was also conducted to provide an overall estimation of risk effects of frequently reported gene variants. This included a subset data of 982 acne cases and 846 controls extracted from our existing GWAS database on various allergic and skin diseases among Singapore Chinese.
RESULTS
Systematic review of 51 articles covering Asians and Caucasians found 60 genes/loci and their 100 variants implicated in acne; majority of them were in the intron, coding region/missense, and promoter regions. The commonly studied candidate genes/gene families include tumor necrosis factor (TNF), and the interleukin (IL) and cytochrome P450 (CYP) gene families. Our meta-analysis showed that most of the analyzed gene variants exhibited insignificant pooled odds ratio (pOR) and significant heterogeneity between studies. Nevertheless, we found that TNF rs1800629 A allele carriers and CYP17A1 rs743572 T allele carriers had significantly reduced mild acne risk [pOR: 0.60; 95% Confidence Interval (CI): 0.33-0.86] and severe acne risk (pOR: 0.59; 95% CI: 0.40-0.79), respectively, across populations. Overall, FST (follistatin) rs629725 A allele poses a significantly modest increased risk for acne presentation (pOR: 1.19, 95% CI: 1.14, 1.23), but neither TIMP2 (TIMP metallopeptidase inhibitor 2) rs8179090 nor CYP1A1 rs4646903 (pOR: 0.96, 95% CI: 0.80-1.12; pOR: 0.95, 95% CI: 0.83, 1.08), respectively. We discovered 15 novel SNPs in the 3' UTR region of the Toll-like Receptor 4 gene (TLR4) associated with acne presentation.
CONCLUSIONS
This systematic review and meta-analysis suggest that genes influencing inflammatory responses, specifically TNF, and genes influencing the function and activity of sebaceous glands, specifically CYP17A1 and FST, have potential risk variants for acne presentation and severity across populations. Understanding the genetic susceptibility factors and biological pathways involved in the pathogenesis of acne will help us to gain insights into developing effective acne treatments.
Topics: Acne Vulgaris; Alleles; Genetic Predisposition to Disease; Humans; Polymorphism, Single Nucleotide
PubMed: 33849530
DOI: 10.1186/s12920-021-00953-8