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1.
Int J Infect Dis ; 2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-34958931

RESUMO

BACKGROUND: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare, serious complication after adenoviral COVID-19 vaccine administration that can involve various organ systems. We aimed to investigate the clinical significance of hepatosplenic thrombosis in patients with VITT. METHODS: We searched PubMed ePubs, Scopus, Embase, and Web of Science databases for studies published until April 28, 2021 involving patients with VITT after ChAdOx1 nCoV-19 vaccination. Demographic and clinical characteristics including laboratory measurements were collected and compared. RESULTS: Four case series and three case reports involving 48 cases of VITT were included. Hepatosplenic thrombosis was present in eight cases (17%). Patients with hepatosplenic thrombosis had lower platelet counts (13,000 vs. 29,500/µL, p=0.016) and higher D-dimer levels (140.0 vs. 57.3 times upper limit of normal range, p=0.028). Multiple-site thrombosis was also associated with hepatosplenic thrombosis (88% vs. 15%, p<0.001). CONCLUSIONS: This is the first study comparing clinical profiles of patients with VITT according to the presence of hepatosplenic thrombosis. Patients with hepatosplenic thrombosis had more severe presentations with lower platelet counts, higher D-dimer levels, and higher rate of multiple-site thromboses. Further studies with larger sample sizes are required to establish definitive evidence regarding the significance of hepatosplenic thrombosis in VITT.

2.
Clin Transl Sci ; 2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34719115

RESUMO

On October 2020, the US Food and Drug Administration (FDA) approved remdesivir as the first drug for the treatment of coronavirus disease 2019 (COVID-19), increasing remdesivir prescriptions worldwide. However, potential cardiovascular (CV) toxicities associated with remdesivir remain unknown. We aimed to characterize the CV adverse drug reactions (ADRs) associated with remdesivir using VigiBase, an individual case safety report database of the World Health Organization (WHO). Disproportionality analyses of CV-ADRs associated with remdesivir were performed using reported odds ratios and information components. We conducted in vitro experiments using cardiomyocytes derived from human pluripotent stem cell cardiomyocytes (hPSC-CMs) to confirm cardiotoxicity of remdesivir. To distinguish drug-induced CV-ADRs from COVID-19 effects, we restricted analyses to patients with COVID-19 and found that, after adjusting for multiple confounders, cardiac arrest (adjusted odds ratio [aOR]: 1.88, 95% confidence interval [CI]: 1.08-3.29), bradycardia (aOR: 2.09, 95% CI: 1.24-3.53), and hypotension (aOR: 1.67, 95% CI: 1.03-2.73) were associated with remdesivir. In vitro data demonstrated that remdesivir reduced the cell viability of hPSC-CMs in time- and dose-dependent manners. Physicians should be aware of potential CV consequences following remdesivir use and implement adequate CV monitoring to maintain a tolerable safety margin.

3.
J Med Virol ; 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34709664

RESUMO

Two messenger RNA (mRNA) vaccines developed by Pfizer-BioNTech and Moderna are being rolled out. Despite the high volume of emerging evidence regarding adverse events (AEs) associated with the COVID-19 mRNA vaccines, previous studies have thus far been largely based on the comparison between vaccinated and unvaccinated control, possibly highlighting the AE risks with COVID-19 mRNA vaccination. Comparing the safety profile of mRNA vaccinated individuals with otherwise vaccinated individuals would enable a more relevant assessment for the safety of mRNA vaccination. We designed a comparative safety study between 18 755 and 27 895 individuals who reported to VigiBase for adverse events following immunization (AEFI) with mRNA COVID-19 and influenza vaccines, respectively, from January 1, 2020, to January 17, 2021. We employed disproportionality analysis to rapidly detect relevant safety signals and compared comparative risks of a diverse span of AEFIs for the vaccines. The safety profile of novel mRNA vaccines was divergent from that of influenza vaccines. The overall pattern suggested that systematic reactions like chill, myalgia, fatigue were more noticeable with the mRNA COVID-19 vaccine, while injection site reactogenicity events were more prevalent with the influenza vaccine. Compared to the influenza vaccine, mRNA COVID-19 vaccines demonstrated a significantly higher risk for a few manageable cardiovascular complications, such as hypertensive crisis (adjusted reporting odds ratio [ROR], 12.72; 95% confidence interval [CI], 2.47-65.54), and supraventricular tachycardia (adjusted ROR, 7.94; 95% CI, 2.62-24.00), but lower risk of neurological complications such as syncope, neuralgia, loss of consciousness, Guillain-Barre syndrome, gait disturbance, visual impairment, and dyskinesia. This study has not identified significant safety concerns regarding mRNA vaccination in real-world settings. The overall safety profile patterned a lower risk of serious AEFI following mRNA vaccines compared to influenza vaccines.

4.
J Autoimmun ; 122: 102681, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34139631

RESUMO

Cerebral venous thrombosis (CVT) events have been reported after vaccination with adenoviral COVID-19 vector vaccines. This study aimed to compare the clinical presentations and courses of vaccine-induced thrombotic thrombocytopenia (VITT) between the two adenoviral vector vaccines, Ad26.COV.2.S (Janssen/Johnson & Johnson) and ChAdOx1 nCoV-19 (Astra-Zeneca). We found that CVT after Ad26.COV.2.S vaccination presents later with similar symptoms compared to CVT after administration of ChAdOx1 nCoV-19, albeit with more thrombosis and intracerebral hemorrhage, lower D-dimer and aPTT levels but similar mortality. These findings could help guide clinical assessment and management of CVT after COVID-19 vaccination.


Assuntos
Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Trombose Venosa/etiologia , Humanos , SARS-CoV-2 , Trombose Venosa/epidemiologia
5.
Int J Biol Sci ; 17(8): 2112-2123, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34131410

RESUMO

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract that mainly affects young people. IBD is associated with various gastrointestinal symptoms, and thus, affects the quality of life of patients. Currently, the pathogenesis of IBD is poorly understood. Although intestinal bacteria and host immune response are thought to be major factors in its pathogenesis, a sufficient explanation of their role in its pathophysiologic mechanism has not been presented. MicroRNAs (miRNAs), which are small RNA molecules that regulate gene expression, have gained attention as they are known to participate in the molecular interactions of IBD. Recent studies have confirmed the important role of miRNAs in targeting certain molecules in signaling pathways that regulate the homeostasis of the intestinal barrier, inflammatory reactions, and autophagy of the intestinal epithelium. Several studies have identified the specific miRNAs associated with IBD from colon tissues or serum samples of IBD patients and have attempted to use them as useful diagnostic biomarkers. Furthermore, some studies have attempted to treat IBD through intracolonic administration of specific miRNAs in the form of nanoparticle. This review summarizes the latest findings on the role of miRNAs in the pathogenesis, diagnosis, and treatment of IBD.

6.
Clin Gastroenterol Hepatol ; 19(9): 1970-1972.e3, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33940227

RESUMO

Remdesivir has demonstrated clinical benefits in randomized placebo-controlled trials (RCTs) in patients with coronavirus disease 2019 (COVID-19)1-4 and was first approved for COVID-19 patients.5 However, whether remdesivir causes gastrointestinal adverse drug reaction (GI-ADRs) including hepatotoxicity is less clear.1-4,6 Therefore, we aimed to detect a diverse spectrum of GI-ADRs associated with remdesivir using VigiBase, the World Health Organization's international pharmacovigilance database of individual case safety reports.


Assuntos
COVID-19 , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Monofosfato de Adenosina/análogos & derivados , Sistemas de Notificação de Reações Adversas a Medicamentos , Alanina/análogos & derivados , COVID-19/tratamento farmacológico , Bases de Dados Factuais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Humanos , Farmacovigilância , SARS-CoV-2 , Organização Mundial da Saúde
7.
Semin Arthritis Rheum ; 51(3): 513-522, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33866147

RESUMO

The incidence of autoimmune diseases is increasing worldwide, thus stimulating studies on their etiopathogenesis, derived from a complex interaction between genetic and environmental factors. Genetic association studies have shown the PTPN22 gene as a shared genetic risk factor with implications in multiple autoimmune disorders. By encoding a protein tyrosine phosphatase expressed by the majority of cells belonging to the innate and adaptive immune systems, the PTPN22 gene may have a fundamental role in the development of immune dysfunction. PTPN22 polymorphisms are associated with rheumatoid arthritis, type 1 diabetes, systemic lupus erythematosus, and many other autoimmune conditions. In this review, we discuss the progress in our understanding of how PTPN22 impacts autoimmunity in both humans and animal models. In addition, we highlight the pathogenic significance of the PTPN22 gene, with particular emphasis on its role in T and B cells, and its function in innate immune cells, such as monocytes, dendritic and natural killer cells. We focus particularly on the complexity of PTPN22 interplay with biological processes of the immune system. Findings highlight the importance of studying the function of disease-associated PTPN22 variants in different cell types and open new avenues of investigation with the potential to drive further insights into mechanisms of PTPN22. These new insights will reveal important clues to the molecular mechanisms of prevalent autoimmune diseases and propose new potential therapeutic targets.


Assuntos
Artrite Reumatoide , Doenças Autoimunes , Lúpus Eritematoso Sistêmico , Animais , Doenças Autoimunes/genética , Autoimunidade , Linfócitos B , Predisposição Genética para Doença , Humanos , Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Nucleotídeo Único , Proteína Tirosina Fosfatase não Receptora Tipo 22/genética
8.
Int J Biol Sci ; 16(15): 2906-2923, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061805

RESUMO

In December 2019, an acute respiratory disease caused by novel species of coronavirus (SARS-CoV-2), emerged in China and has spread throughout the world. On 11th March 2020, the World Health Organization (WHO) officially declared coronavirus disease 19 (COVID-19) a pandemic, severe coronavirus-mediated human disease. Based on genomic and phylogenetic studies, SARS-CoV-2 might originate from bat coronaviruses and infects humans directly or through intermediate zoonotic hosts. However, the exact origin or the host intermediate remains unknown. Genetically, SARS-CoV-2 is similar to several existing coronaviruses, particularly SARS-CoV, but differs by silent and non-silent mutations. The virus uses different transmission routes and targets cells and tissues with angiotensin-converting enzyme 2 (ACE2) protein, which makes it contagious. COVID-19 shares both the main clinical features and excessive/dysregulated cell responses with the two previous Middle East respiratory syndrome coronavirus (MERS) and severe acute respiratory syndrome coronavirus (SARS) epidemics. In this review, we provide an update of the current knowledge on the COVID-19 pandemic. Gaining a deeper understanding of SARS-CoV-2 structure, transmission routes, and molecular responses, will assist in the prevention and control of COVID-19 outbreaks in the future.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/transmissão , Pneumonia Viral/imunologia , Pneumonia Viral/transmissão , Enzima de Conversão de Angiotensina 2 , Animais , COVID-19 , Teste para COVID-19 , China/epidemiologia , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Genômica , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio , Pandemias , Peptidil Dipeptidase A/metabolismo , Filogenia , SARS-CoV-2
9.
Brain Sci ; 10(10)2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33007889

RESUMO

This study aimed to verify noteworthy findings between genetic risk factors and autism spectrum disorder (ASD) by employing the false positive report probability (FPRP) and the Bayesian false-discovery probability (BFDP). PubMed and the Genome-Wide Association Studies (GWAS) catalog were searched from inception to 1 August, 2019. We included meta-analyses on genetic factors of ASD of any study design. Overall, twenty-seven meta-analyses articles from literature searches, and four manually added articles from the GWAS catalog were re-analyzed. This showed that five of 31 comparisons for meta-analyses of observational studies, 40 out of 203 comparisons for the GWAS meta-analyses, and 18 out of 20 comparisons for the GWAS catalog, respectively, had noteworthy estimations under both Bayesian approaches. In this study, we found noteworthy genetic comparisons highly related to an increased risk of ASD. Multiple genetic comparisons were shown to be associated with ASD risk; however, genuine associations should be carefully verified and understood.

10.
Int J Mol Sci ; 21(19)2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33008138

RESUMO

Eosinophilic esophagitis (EoE) is a relatively new condition described as an allergic-mediated disease of the esophagus. Clinically, it is characterized by dysphagia, food impaction, and reflux-like symptoms. Multiple genome-wide association studies (GWAS) have been conducted to identify genetic loci associated with EoE. The integration of numerous studies investigating the genetic polymorphisms in EoE and the Mendelian diseases associated with EoE are discussed to provide insights into the genetic risk of EoE, notably focusing on CCL26 and CAPN14. We focus on the genetic loci investigated thus far, and their classification according to whether the function near the loci is known. The pathophysiology of EoE is described by separately presenting the known function of each cell and molecule, with the major contributors being eosinophils, Th2 cells, thymic stromal lymphopoietin (TSLP), transforming growth factor (TGF)-ß1, and interleukin (IL)-13. This review aims to provide detailed descriptions of the genetics and the comprehensive pathophysiology of EoE.


Assuntos
Calpaína/genética , Quimiocina CCL26/genética , Esofagite Eosinofílica/genética , Predisposição Genética para Doença , Citocinas/genética , Esofagite Eosinofílica/patologia , Esôfago/patologia , Estudo de Associação Genômica Ampla , Humanos , Hipersensibilidade/complicações , Hipersensibilidade/genética , Interleucina-13/genética , Células Th2/metabolismo , Fator de Crescimento Transformador beta1/genética
11.
Int J Mol Sci ; 21(19)2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33023023

RESUMO

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune disorder which affects small- and, to a lesser degree, medium-sized vessels. ANCA-associated vasculitis encompasses three disease phenotypes: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). This classification is largely based on clinical presentations and has several limitations. Recent research provided evidence that genetic background, risk of relapse, prognosis, and co-morbidities are more closely related to the ANCA serotype, proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA, compared to the disease phenotypes GPA or MPA. This finding has been extended to the investigation of biomarkers predicting disease activity, which again more closely relate to the ANCA serotype. Discoveries related to the immunopathogenesis translated into clinical practice as targeted therapies are on the rise. This review will summarize the current understanding of the immunopathogenesis of ANCA-associated vasculitis and the interplay between ANCA serotype and proposed disease biomarkers and illustrate how the extending knowledge of the immunopathogenesis will likely translate into development of a personalized medicine approach in the management of ANCA-associated vasculitis.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/genética , Anticorpos Anticitoplasma de Neutrófilos/genética , Mieloblastina/genética , Peroxidase/genética , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/classificação , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Anticorpos Anticitoplasma de Neutrófilos/sangue , Biomarcadores/sangue , Síndrome de Churg-Strauss/sangue , Síndrome de Churg-Strauss/genética , Síndrome de Churg-Strauss/patologia , Granulomatose com Poliangiite/sangue , Granulomatose com Poliangiite/genética , Granulomatose com Poliangiite/patologia , Humanos , Poliangiite Microscópica/sangue , Poliangiite Microscópica/genética , Poliangiite Microscópica/patologia , Prognóstico , Sorogrupo
12.
Int J Mol Sci ; 21(16)2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32784808

RESUMO

Sarcopenia refers to a decrease in skeletal muscle mass and function. Because sarcopenia affects mortality, and causes significant disability, the clinical importance of sarcopenia is emerging. At first, sarcopenia was recognized as an age-related disease but, recently, it has been reported to be prevalent also in younger patients with autoimmune diseases. Specifically, the association of sarcopenia and autoimmune diseases such as rheumatoid arthritis has been studied in detail. Although the pathogenesis of sarcopenia in autoimmune diseases has not been elucidated, chronic inflammation is believed to contribute to sarcopenia, and moreover the pathogenesis seems to be different depending on the respective underlying disease. The definition of sarcopenia differs among studies, which limits direct comparisons. Therefore, in this review, we cover various definitions of sarcopenia used in previous studies and highlight the prevalence of sarcopenia in diverse autoimmune diseases including rheumatoid arthritis, spondyloarthritis, systemic sclerosis, inflammatory bowel disease, and autoimmune diabetes. In addition, we cover the pathogenesis and treatment of sarcopenia in autoimmune and rheumatic diseases. This review provides a comprehensive understanding of sarcopenia in various autoimmune diseases and highlights the need for a consistent definition of sarcopenia.


Assuntos
Doenças Autoimunes/complicações , Doenças Reumáticas/complicações , Sarcopenia/complicações , Humanos , Modelos Biológicos , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia
13.
Cytokine ; 134: 155206, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32683104

RESUMO

The interleukin-26 (IL-26), a member of the IL-10 family is one of the latest discovered cytokines which contributes in numerous chronic autoimmune and inflammatory disorders. In the current case-control study, we investigated the distribution of three IL-26 single nucleotide polymorphisms (SNPs) (rs7134599, rs2870946 & rs1558744) in 440 Tunisian adults via Taqman genotyping assay. The presence of rs7134599 and rs1558744 polymorphisms considerably reduced the risk of developing asthma while the rs7134599 AA [OR = 0.40, CI: 0.23-0.70] and AG [OR = 0.50, CI (0.32-0.76)] genotypes protected against the asthma risk. The rs7134599 A allele was correlated with a lower risk of developing severe asthma (p < 0.001) while that of the rs2870946 CC genotype was associated with a higher risk of developing asthma in smoking patients (p < 0.001). In addition, we measured the IL-26 levels in the serum by an Enzyme-linked-Immunosorbent Assay (ELISA). During the analysis, we found that IL-26 serum levels were incredibly increased in asthmatic patients compared to the healthy controls. Our study revealed a significant association of IL-26 gene polymorphisms with asthma for the first time which can serve as biomarkers for asthma in the Tunisian population. The significant increase of IL-26 serum protein levels in asthma patients suggested a major role of IL-26 in asthma phenotypes.


Assuntos
Asma/genética , Asma/imunologia , Interleucinas/genética , Polimorfismo de Nucleotídeo Único , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Haplótipos , Humanos , Interleucinas/sangue , Masculino , Pessoa de Meia-Idade , Tunísia
14.
J Clin Med ; 9(8)2020 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-32726951

RESUMO

(1) Background: The use of corticosteroids in critical coronavirus infections, including severe acute respiratory syndrome (SARS), Middle East Respiratory Syndrome (MERS), or Coronavirus disease 2019 (COVID-19), has been controversial. However, a meta-analysis on the efficacy of steroids in treating these coronavirus infections is lacking. (2) Purpose: We assessed a methodological criticism on the quality of previous published meta-analyses and the risk of misleading conclusions with important therapeutic consequences. We also examined the evidence of the efficacy of corticosteroids in reducing mortality in SARS, MERS and COVID-19. (3) Methods: PubMed, MEDLINE, Embase, and Web of Science were used to identify studies published until 25 April 2020, that reported associations between steroid use and mortality in treating SARS/MERS/COVID-19. Two investigators screened and extracted data independently. Searches were restricted to studies on humans, and articles that did not report the exact number of patients in each group or data on mortality were excluded. We calculated odds ratios (ORs) or hazard ratios (HRs) under the fixed- and random-effect model. (4) Results: Eight articles (4051 patients) were eligible for inclusion. Among these selected studies, 3416 patients were diagnosed with SARS, 360 patients with MERS, and 275 with COVID-19; 60.3% patients were administered steroids. The meta-analyses including all studies showed no differences overall in terms of mortality (OR 1.152, 95% CI 0.631-2.101 in the random effects model, p = 0.645). However, this conclusion might be biased, because, in some studies, the patients in the steroid group had more severe symptoms than those in the control group. In contrast, when the meta-analysis was performed restricting only to studies that used appropriate adjustment (e.g., time, disease severity), there was a significant difference between the two groups (HR 0.378, 95% CI 0.221-0.646 in the random effects model, p < 0.0001). Although there was no difference in mortality when steroids were used in severe cases, there was a difference among the group with more underlying diseases (OR 3.133, 95% CI 1.670-5.877, p < 0.001). (5) Conclusions: To our knowledge, this study is the first comprehensive systematic review and meta-analysis providing the most accurate evidence on the effect of steroids in coronavirus infections. If not contraindicated, and in the absence of side effects, the use of steroids should be considered in coronavirus infection including COVID-19.

15.
J Clin Med ; 8(3)2019 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-30871019

RESUMO

The 1858T allele in the protein tyrosine phosphatase non-receptor type 22 (PTPN22) locus shows one of the strongest and most consistent genetic associations with autoimmune diseases. We synthesized all meta-analyses reporting a genetic association of the PTPN22 1858T C/T polymorphism with autoimmune diseases. This work examined their validity to discover false positive results under Bayesian methods. We conducted a PubMed search to identify relevant publications and extracted the respective results, published until 30 November 2018. In observational studies, the associations of 1858 C/T genetic variant were noteworthy for 12 autoimmune or autoimmunity-related diseases (rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes mellitus, juvenile idiopathic arthritis, Crohn's disease, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, vitiligo, Graves' disease, myasthenia gravis, Addison's disease, giant cell arteritis, and endometriosis). In contrast, we could not confirm the noteworthiness for eight diseases (systemic sclerosis, psoriasis, Behçet's disease, autoimmune thyroid disease, alopecia areata, Sjögren's syndrome, inflammatory bowel disease, and ankylosing spondylitis). From the meta-analysis of genome-wide association studies (GWAS) with a p-value < 5 × 10-8, findings verified noteworthiness for all autoimmune diseases (psoriatic arthritis, myasthenia gravis, juvenile idiopathic arthritis and rheumatoid arthritis). The results from meta-analysis of GWAS showing a p-value ranging between 0.05 and 5 × 10-8 were noteworthy under both Bayesian approaches (ANCA-associated vasculitis, type 1 diabetes mellitus, giant cell arteritis and juvenile idiopathic arthritis). Re-analysis of observational studies and GWAS by Bayesian approaches revealed the noteworthiness of all significant associations observed by GWAS, but noteworthiness could not be confirmed for all associations found in observational studies.

17.
Cytokine ; 106: 154-164, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29103823

RESUMO

As a complex disease, multiple sclerosis (MS) susceptibility implicates many genetic and environmental factors. Usually, individual genetic association studies have several limitations, and results are specific to the population of study. The Meta-analysis approach has been proposed to resolve these limitations and to increase the power of statistical analyses. In this review, we summarize results from meta-analyses of candidate genes of MS. Using the keywords: multiple sclerosis, genetic polymorphism and meta-analysis, we searched electronic databases (PubMed, Embase and Web of Sciences) for published meta-analyses until May 2017. Meta-analyses confirmed the association of polymorphisms in fifteen candidate genes with MS disease. However, polymorphisms in fourteen genes showed none significant association. Results outlined the importance of confirmed genes to understand signaling pathways in MS disease and shed light on their utility to develop new drugs targets.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Metanálise como Assunto , Esclerose Múltipla/genética , Humanos , Modelos Biológicos
18.
BMC Neurol ; 17(1): 32, 2017 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-28202008

RESUMO

BACKGROUND: Antiepileptic drugs (AEDs) are effective medications available for epilepsy. However, many patients do not respond to this treatment and become resistant. Genetic polymorphisms may be involved in the variation of AEDs response. Therefore, we conducted an updated systematic review and a meta-analysis to investigate the contribution of the genetic profile on epilepsy drug resistance. METHODS: We proceeded to the selection of eligible studies related to the associations of polymorphisms with resistance to AEDs therapy in epilepsy, published from January 1980 until November 2016, using Pubmed and Cochrane Library databases. The association analysis was based on pooled odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: From 640 articles, we retained 13 articles to evaluate the relationship between ATP-binding cassette sub-family C member 1 (ABCB1) C3435T polymorphism and AEDs responsiveness in a total of 454 epileptic AEDs-resistant cases and 282 AEDs-responsive cases. We found a significant association with an OR of 1.877, 95% CI 1.213-2.905. Subanalysis by genotype model showed a more significant association between the recessive model of ABCB1 C3435T polymorphism (TT vs. CC) and the risk of AEDs resistance with an OR of 2.375, 95% CI 1.775-3.178 than in the dominant one (CC vs. TT) with an OR of 1.686, 95% CI 0.877-3.242. CONCLUSION: Our results indicate that ABCB1 C3435T polymorphism, especially TT genotype, plays an important role in refractory epilepsy. As genetic screening of this genotype may be useful to predict AEDs response before starting the treatment, further investigations should validate the association.


Assuntos
Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Resistência a Medicamentos/genética , Epilepsia/tratamento farmacológico , Epilepsia/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Resistência a Medicamentos/efeitos dos fármacos , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único/genética
19.
Allergy Asthma Immunol Res ; 7(2): 130-40, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25729620

RESUMO

PURPOSE: Asthma is a complex disease, with contributions from multiple genes, various genetic backgrounds, and environmental factors. Many human epidemiological studies have demonstrated that single nucleotide polymorphisms (SNPs) in Toll-like receptor (TLR) genes are inconsistently associated with asthma risk. Some have demonstrated differences concerning the study design and effect size, and conflicting results have been reported. A meta-analysis is necessary to determine the magnitude of this association. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, a systematic search and meta-analysis of the literature was conducted to estimate the association of SNPs in TLR genes with asthma risk. We screened the medical literature based on the following keyword searches in MEDLINE and EMBASE databases: 'TLR', 'polymorphism', 'asthma', and their combinations. RESULTS: Meta-analysis of eight studies on TLR4 Asp299Gly showed a marginal association of TLR4 with asthma risk (odds ratio [OR]=0.814 [95% confidence interval [CI], 0.652-1.016; P=0.069]) in the recessive model. TLR4 Thr399Ile was not associated with asthma risk under any genetic model. Meta-analysis of four studies on TLR2 Arg753Gln indicated that TLR2 might be significantly associated with asthma in the dominant and codominant models (P=0.029, P=0.030, and P=0.009, respectively). TLR9 -1237 was marginally associated with asthma risk (OR=0.408 [95% CI, 0.163-1.021; P=0.065]) in the codominant model. Analysis using the allele contrast model showed that the major TLR9 -1237 T allele tended to be a significant protective factor with OR=0.689 (95% CI, 0.471-1.007; P=0.055). CONCLUSIONS: The results showed that TLR4 Asp299Gly, TLR2 Arg753Gln, and TLR9-1237 might contribute significantly to asthma susceptibility. Future genetic association studies would consolidate these findings.

20.
Immunol Lett ; 164(1): 18-24, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25639450

RESUMO

The human matrix metalloproteinases (MMPs) are importantly involved in aneurysm formation. Since the clinical manifestations in Behçet disease (BD) include aneurysm formation among major symptoms, polymorphisms in MMP-9 might be associated with BD susceptibility. The aim of the current case-control study was to investigate the association of four single nucleotide polymorphisms (SNPs) in MMP-9 gene: -1562 C/T, 2003 G/A (R668Q), 836 A/G (Q279R) and 1721 C/G (R574P) with BD risk in the Tunisian population. The distribution of MMP-9 gene polymorphisms was analyzed by polymerase chain-reaction (PCR) and restriction fragment length polymorphism (RFLP) for 240 BD patients and 288 controls. Our study indicated that the MMP-9 -1562 C/T polymorphism (rs3918242) was not associated with BD risk. We found a significant association of the MMP-9 2003 G/A (rs17577) with an increased susceptibility to BD. However, the MMP-9 1721 C/G polymorphism (rs2250889) had a protective role against the development of BD. Subgroup analysis based on stratification by gender revealed that the MMP-9 2003 G/A polymorphism was associated with a highly significant BD risk in women's group (G vs. A: P=0.0000001). However, the MMP-9 836 A/G polymorphism had a protective role in men's group (G vs. A: P=0.00043). The MMP-9 1721 C/G polymorphism was associated with a protective effect in both men and women groups (CG+GG vs. CC: P=0.04 and P=0.0002, respectively). The haplotype analysis did not show any association with BD risk. A significant difference in the MMP-9 serum levels were observed in the patient subgroup with ocular lesions manifestations.


Assuntos
Síndrome de Behçet/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Metaloproteinase 9 da Matriz/genética , Polimorfismo Genético , Adolescente , Adulto , Alelos , Síndrome de Behçet/sangue , Síndrome de Behçet/patologia , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Metaloproteinase 9 da Matriz/sangue , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único , Risco , Adulto Jovem
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