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Life (Basel, Switzerland) Aug 2023Our aim was to carry out a qualitative and quantitative synthesis of the influence of CCR5 genetic variants on Chagas disease (CD) through a systematic review. A total...
Our aim was to carry out a qualitative and quantitative synthesis of the influence of CCR5 genetic variants on Chagas disease (CD) through a systematic review. A total of 1197 articles were analyzed, and eleven were included in the review. A meta-analysis was conducted along with principal component analyses (PCAs). The polymorphisms found were analyzed using the SNP2TFBS tool to identify possible variants that influence the interaction with gene binding sites. Eleven studied variants were identified: rs2856758, rs2734648, rs1799987, rs1799988, rs41469351, rs1800023, rs1800024, Δ32/rs333, rs3176763, rs3087253 and rs11575815. The studies analyzed were published between 2001 and 2019, conducted in Argentina, Brazil, Spain, Colombia and Venezuela, and included Argentine, Brazilian, Colombian, Peruvian and Venezuelan patients. Eight polymorphisms were subjected to the meta-analysis, of which six were associated with the development of the cardiac form of CD: rs1799987-G/G and G/A in the dominance model and G/G in the recessiveness model; rs2856758-A/G in the codominance model; rs2734648-T/T and T/G in the dominance model; rs1799988-T/T in both the codominance and recessiveness models; rs1800023-G allele and the G/G genotype in the codominance and recessiveness models, and the G/G and G/A genotypes in the dominance model; and rs1800024-T allele. The PCA analyses were able to indicate the relationships between the alleles and the genotypes of the polymorphisms. The SNP2TFBS tool identified rs1800023 as an influencer of the Spi1 transcription factor ( < 0.05). A correlation was established between the alleles associated with the cardiac form of CD in this review, members of the C haplotype of the gene (HHC-TGTG), and the cardiac form of CD.
PubMed: 37629534
DOI: 10.3390/life13081677 -
BMJ Global Health Feb 2024Limited information on costs and the cost-effectiveness of hospital interventions to reduce antibiotic resistance (ABR) hinder efficient resource allocation.
Costs-effectiveness and cost components of pharmaceutical and non-pharmaceutical interventions affecting antibiotic resistance outcomes in hospital patients: a systematic literature review.
INTRODUCTION
Limited information on costs and the cost-effectiveness of hospital interventions to reduce antibiotic resistance (ABR) hinder efficient resource allocation.
METHODS
We conducted a systematic literature review for studies evaluating the costs and cost-effectiveness of pharmaceutical and non-pharmaceutical interventions aimed at reducing, monitoring and controlling ABR in patients. Articles published until 12 December 2023 were explored using EconLit, EMBASE and PubMed. We focused on critical or high-priority bacteria, as defined by the WHO, and intervention costs and incremental cost-effectiveness ratio (ICER). Following Preferred Reporting Items for Systematic review and Meta-Analysis guidelines, we extracted unit costs, ICERs and essential study information including country, intervention, bacteria-drug combination, discount rates, type of model and outcomes. Costs were reported in 2022 US dollars ($), adopting the healthcare system perspective. Country willingness-to-pay (WTP) thresholds from Woods 2016 guided cost-effectiveness assessments. We assessed the studies reporting checklist using Drummond's method.
RESULTS
Among 20 958 articles, 59 (32 pharmaceutical and 27 non-pharmaceutical interventions) met the inclusion criteria. Non-pharmaceutical interventions, such as hygiene measures, had unit costs as low as $1 per patient, contrasting with generally higher pharmaceutical intervention costs. Several studies found that linezolid-based treatments for methicillin-resistant were cost-effective compared with vancomycin (ICER up to $21 488 per treatment success, all 16 studies' ICERs
CONCLUSION
Robust information on ABR interventions is critical for efficient resource allocation. We highlight cost-effective strategies for mitigating ABR in hospitals, emphasising substantial knowledge gaps, especially in low-income and middle-income countries. Our study serves as a resource for guiding future cost-effectiveness study design and analyses. CRD42020341827 and CRD42022340064.
Topics: Humans; Methicillin-Resistant Staphylococcus aureus; Checklist; Drug Resistance, Microbial; Hospitals; Pharmaceutical Preparations
PubMed: 38423548
DOI: 10.1136/bmjgh-2023-013205 -
Molecular Genetics & Genomic Medicine Nov 2023Among present reports, the T/G allelic variation at the rs2609255 locus of the family sequence similarity gene 13A (FAM13A) was considerable associated with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Among present reports, the T/G allelic variation at the rs2609255 locus of the family sequence similarity gene 13A (FAM13A) was considerable associated with susceptibility to interstitial lung diseases (ILDs). In this study, we summarized relevant studies and applied a meta-analysis to explore whether the polymorphism of rs2609255 site of the FAM13A gene can be utilized to predict susceptibility to idiopathic pulmonary fibrosis (IPF) patients or rheumatoid arthritis-associated interstitial lung disease (RA-ILD) or silicosis patients in different populations for the first time.
METHODS
We compared the frequency of G allele on rs2609255 site of FAM13A between the control subjects and IPF or RA-ILD or silicosis patients from different races by using meta-analysis. Nine studies were involved in this meta-analysis, including five IPF studies, two RA-ILD studies, and two silicosis studies, and containing 14 subgroups. We conducted separate meta-analyses for different races.
RESULTS
In all individuals, a substantial link between the G allele of the FAM13A rs2609255 polymorphism and IPF (OR: 1.47, 95% CI: 1.33-1.63, p < 0.00001) was indicated. After dividing by ethnicity, the G allele was illustrated to be considerable correlation with IPF in Asian (OR: 2.63, 95% CI: 1.81-3.81, p < 0.00001) and with RA-ILD individuals (OR: 3.27, 95% CI: 1.26-8.49, p = 0.01). Conversely, there was no correlation with the G allele and IPF in European individuals (OR: 1.27, 95% CI: 0.89-1.83, p = 0.13) or silicosis in Chinese individuals (OR: 1.20, 95% CI: 0.99-1.46, p = 0.07).
CONCLUSION
This is the first meta-analysis that provides evidence that the rs2609255 of FAM13A might increase susceptibility to RA-ILD, and IPF especially in Asian but not in European individuals, and not be correlated with silicosis in Chinese individuals, which indicated the differences in susceptibility to disease by race were noteworthy.
Topics: Humans; Lung Diseases, Interstitial; Idiopathic Pulmonary Fibrosis; Polymorphism, Genetic; Arthritis, Rheumatoid; Silicosis; GTPase-Activating Proteins
PubMed: 37786320
DOI: 10.1002/mgg3.2279 -
Journal of Medical Genetics Dec 2023Alström syndrome (ALMS; #203800) is an ultrarare monogenic recessive disease. This syndrome is associated with variants in the gene, which encodes a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Alström syndrome (ALMS; #203800) is an ultrarare monogenic recessive disease. This syndrome is associated with variants in the gene, which encodes a centrosome-associated protein involved in the regulation of several ciliary and extraciliary processes, such as centrosome cohesion, apoptosis, cell cycle control and receptor trafficking. The type of variant associated with ALMS is mostly complete loss-of-function variants (97%) and they are mainly located in exons 8, 10 and 16 of the gene. Other studies in the literature have tried to establish a genotype-phenotype correlation in this syndrome with limited success. The difficulty in recruiting a large cohort in rare diseases is the main barrier to conducting this type of study.
METHODS
In this study we collected all cases of ALMS published to date. We created a database of patients who had a genetic diagnosis and an individualised clinical history. Lastly, we attempted to establish a genotype-phenotype correlation using the truncation site of the patient's longest allele as a grouping criteria.
RESULTS
We collected a total of 357 patients, of whom 227 had complete clinical information, complete genetic diagnosis and meta-information on sex and age. We have seen that there are five variants with high frequency, with p.(Arg2722Ter) being the most common variant, with 28 alleles. No gender differences in disease progression were detected. Finally, truncating variants in exon 10 seem to be correlated with a higher prevalence of liver disorders in patients with ALMS.
CONCLUSION
Pathogenic variants in exon 10 of the gene were associated with a higher prevalence of liver disease. However, the location of the variant in the gene does not have a major impact on the phenotype developed by the patient.
Topics: Humans; Alstrom Syndrome; Cell Cycle Proteins; Phenotype; Exons; Genetic Association Studies
PubMed: 37321834
DOI: 10.1136/jmg-2023-109175 -
Reumatologia Clinica 2023To describe the demographic and clinical features, as well as the frequency of the HLA-B*51 allele in Behçet disease (BD) patients in Latin American countries. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To describe the demographic and clinical features, as well as the frequency of the HLA-B*51 allele in Behçet disease (BD) patients in Latin American countries.
METHODS
A systematic literature review of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines was conducted without performing a meta-analysis. We included observational studies (cross-sectional or cohort) of BD patients fulfilling the International Study Group for BD classification criteria and reported the demographic, clinical, and laboratory features of the disease in adult patients.
RESULTS
Twelve studies were included in the SLR. Information from 532 patients across 5 Latin American countries was included for the analysis. Mean age at disease diagnosis was 33 years, 58.3% were female and 41.7% male; most patients were non-Caucasian. The most common clinical manifestations were recurrent oral ulcers and genital ulcers, followed by skin, eye, joint, neurological, gastrointestinal, vascular, and cardiac involvement. The prevalence of BD was described in 2 studies, 1 conducted in Brazil that reported a prevalence of .3/100,000 inhabitants, and another in Colombia with a prevalence of 1.1/100,000 inhabitants. The frequency of HLA-B*51 allele in BD patients was 38%, 30.1%, and 9% in Argentina, Brazil, and Mexico, respectively.
CONCLUSIONS
The prevalence of BD in the Latin American countries seems to be low, as well as the frequency of HLA-B*51 allele. However, the strength of association between HLA-B*51 and BD remains high in our population. The key clinical features of BD are like those reported in countries/regions where BD is endemic.
Topics: Adult; Humans; Male; Female; Behcet Syndrome; Cross-Sectional Studies; Latin America; HLA-B Antigens; Prevalence
PubMed: 37661116
DOI: 10.1016/j.reumae.2022.12.005 -
Acta Bio-medica : Atenei Parmensis Aug 2023To investigate the association between CYP17A1 (rs74357) polymorphism and the risk of Polycystic Ovary Syndrome (PCOS). (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIM
To investigate the association between CYP17A1 (rs74357) polymorphism and the risk of Polycystic Ovary Syndrome (PCOS).
METHODS
Literature on the association of CYP17rs74357 gene polymorphism and susceptibility to PCOS was retrieved by searching databases such as PubMed, Science Direct, Google Scholar and Embase from. The association measure was analyzed using an Odds Ratio (OR) and 95% Confidence Interval (CI). All the statistical analyses were executed using CMA 3.0 Software.
RESULTS
In the present meta-analysis,24 studies including 3462 PCOS and 2898 controls were analyzed. The overall results validated that the 17 CYP17 T/C (rs74357) gene polymorphism was significantly associated with PCOS risk in 5 genetic models: recessive model (fixed and random effect), dominant model (random effect), CC vs. TT (fixed effect), CT vs. TT (fixed effect), and allele contrast (random effect). Stratified analyses by ethnicity/country also detected significant association between Asian and Caucasian under the recessive, dominant, CC vs. TT, CC vs. CT, and the allele contrast models.
CONCLUSIONS
In the present study, CYP17 T/C (rs74357) gene polymorphism increase the susceptibility of PCOS, and the recessive C allele, can be proposed as a predictive factor for the risk of PCOS or an important pathway in PCOS associated metabolic and hormonal dysregulation especially insulin resistance.However, larger sample size andmultiracial studies are needed in the future to confirm the findings.
Topics: Female; Humans; Genetic Predisposition to Disease; Polycystic Ovary Syndrome; Polymorphism, Genetic; Steroid 17-alpha-Hydroxylase
PubMed: 37539608
DOI: 10.23750/abm.v94i4.14229 -
Annals of Hematology Jun 2024Janus kinase 2 (JAK2) V617F mutation is present in most patients with polycythemia vera (PV). One persistently puzzling aspect unresolved is the association between... (Meta-Analysis)
Meta-Analysis
Janus kinase 2 (JAK2) V617F mutation is present in most patients with polycythemia vera (PV). One persistently puzzling aspect unresolved is the association between JAK2V617F allele burden (also known as variant allele frequency) and the relevant clinical characteristics. Numerous studies have reported associations between allele burden and both hematologic and clinical features. While there are strong indications linking high allele burden in PV patients with symptoms and clinical characteristics, not all associations are definitive, and disparate and contradictory findings have been reported. Hence, this study aimed to synthesize existing data from the literature to better understand the association between JAK2V617F allele burden and relevant clinical correlates. Out of the 1,851 studies identified, 39 studies provided evidence related to the association between JAK2V617F allele burden and clinical correlates, and 21 studies were included in meta-analyses. Meta-analyses of correlation demonstrated that leucocyte and erythrocyte counts were significantly and positively correlated with JAK2V617F allele burden, whereas platelet count was not. Meta-analyses of standardized mean difference demonstrated that leucocyte and hematocrit were significantly higher in patients with higher JAK2V617F allele burden, whereas platelet count was significantly lower. Meta-analyses of odds ratio demonstrated that patients who had higher JAK2V617F allele burden had a significantly greater odds ratio for developing pruritus, splenomegaly, thrombosis, myelofibrosis, and acute myeloid leukemia. Our study integrates data from approximately 5,462 patients, contributing insights into the association between JAK2V617F allele burden and various hematological parameters, symptomatic manifestations, and complications. However, varied methods of data presentation and statistical analyses prevented the execution of high-quality meta-analyses.
Topics: Polycythemia Vera; Janus Kinase 2; Humans; Alleles; Gene Frequency; Amino Acid Substitution; Mutation, Missense
PubMed: 38652240
DOI: 10.1007/s00277-024-05754-4 -
Open Heart Nov 2023Clopidogrel is a P2Y inhibitor that has become a mainstay treatment following percutaneous intervention with drug-eluting stent placement to decrease restenosis and its...
INTRODUCTION
Clopidogrel is a P2Y inhibitor that has become a mainstay treatment following percutaneous intervention with drug-eluting stent placement to decrease restenosis and its potential complications, including sudden cardiac death and ischaemic strokes in patients with significant vascular disease.
AREAS COVERED
As a prodrug, the metabolism and efficacy of clopidogrel are contingent on the presence of wild-type CYP450 (CYP2C19) alleles. Genetic polymorphisms and variants are well known to impair its ability to prevent major adverse cardiovascular events in these patients, with inadequate response rates as high as 30% in previous publications. Patterns of allelic frequencies are expected to exhibit similarities between individuals of the same ancestry, ethnic group or geographic region. Accordingly, we seek to further elucidate worldwide prevalence rates for genetic polymorphisms in the CYP2C19-dependent metabolism of clopidogrel and review the potential of personalised CYP2C19 genotyping in clinical practice to mitigate this high treatment resistance and its associated burden on patients.
EXPERTS' COMMENTARY
Our findings support the consideration of genotyping before initiation of therapy to guide adequate dosage or substitutions of other P2Y inhibitors to promote personalised, precision medicine and to prevent adverse events when these therapies may inevitably fail in patients with variants of the CYP450 (CYP2C19) system.
Topics: Humans; Clopidogrel; Platelet Aggregation Inhibitors; Cytochrome P-450 CYP2C19; Drug-Eluting Stents; Polymorphism, Genetic
PubMed: 37963685
DOI: 10.1136/openhrt-2023-002436 -
The Journal of Prevention of... 2024In patients with Alzheimer's disease pathophysiological changes of the brain that initiate the onset of Alzheimer's disease include accumulation of amyloid-β plaques... (Review)
Review
In patients with Alzheimer's disease pathophysiological changes of the brain that initiate the onset of Alzheimer's disease include accumulation of amyloid-β plaques and phosphorylation of tau-tangles. A rather recently considered risk factor for the onset of Alzheimer's disease is poor oral health. The aim of this systematic review of the literature was to assess the potential association(s) of oral health as a risk factor for the onset of Alzheimer's disease. After a systematic search of Pubmed, Embase and Web of Science. A total of 1962 studies were assessed, of which 17 studies demonstrated possible associations between oral health diseases and Alzheimer's disease. 4 theories could be distinguished that describe the possible links between oral health and the development or onset of Alzheimer's disease; 1) role of pathogens, 2) role of inflammatory mediators, 3) role of APOE alleles and 4) role of Aβ peptide. The main common denominator of all the theories is the neuroinflammation due to poor oral health. Yet, there is insufficient evidence to prove a link due to the diversity of the designs used and the quality of the study design of the included studies. Therefore, further research is needed to find causal links between oral health and neuroinflammation that possibly can lead to the onset of Alzheimer's disease with the future intention to prevent cognitive decline by better dental care.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Neuroinflammatory Diseases; Oral Health; Risk Factors
PubMed: 38230738
DOI: 10.14283/jpad.2023.82 -
Heliyon Jul 2023Psoriasis is a disease with an immunogenetic background in which cytokines have important effects on its prevalence and incidence. The present meta-analysis evaluated...
OBJECTIVE
Psoriasis is a disease with an immunogenetic background in which cytokines have important effects on its prevalence and incidence. The present meta-analysis evaluated the relationship between () polymorphisms (, , , , and ) and psoriasis risk in studies following Hardy-Weinberg equilibrium (HWE).
MATERIALS AND METHODS
Four databases were searched to retrieve relevant studies reporting the distributions of polymorphisms in psoriasis cases compared to controls. The effect sizes were the 95% confidence intervals (CIs) and odds ratios (ORs). Subgroup analysis, sensitivity analyses, publication bias, trial sequential analysis (TSA), and meta-regression were performed on the initial pooled results of polymorphisms.
RESULTS
Thirty-six articles with 71 studies were included in the meta-analysis (twenty-six: 361525, twenty-seven: 1800629, nine: 1799724, four: , and five: 1799964). The pooled ORs for -238 G/A 361525 polymorphism were 2.33 ( < 0.00001), 2.79 ( < 0.0001), 2.35 ( < 0.00001), 2.44 ( < 0.00001), and 2.45 ( < 0.00001), as well as 1.57 ( < 0.00001), 1.98 ( = 0.01), 1.61 ( < 0.00001), 1.64 ( < 0.00001), and 1.79 ( < 0.00001) for -857 C/T 1799724 polymorphism in allelic, homozygous, heterozygous, dominant, and recessive models, respectively. Ethnicity, psoriasis type, and sample size affected the pooled results of 361525, 1800629, and 1799724 polymorphisms. Based on TSA, there were just sufficient cases for -238 G/A 361525 polymorphism in five genetic models and -857C/T 1799724 polymorphism in allelic, heterozygous, and dominant models.
CONCLUSIONS
The A allele and GA and GG genotypes of -238 G/A 361525 polymorphism and T allele, TT and CT genotypes of -857C/T 1799724 polymorphism were related to increased risks in psoriasis cases. Well-designed studies (with no deviation from HWE in controls) with more cases are recommended in the future.
PubMed: 37456021
DOI: 10.1016/j.heliyon.2023.e17552