Publications by authors named "Luydson Richardson Silva Vasconcelos"

26 Publications

  • Page 1 of 1

The role of Mannose-binding lectin in leprosy: A systematic review.

Infect Genet Evol 2021 May 27;93:104945. Epub 2021 May 27.

Department of Medicine, Federal University of Alagoas (UFAL), Arapiraca, Brazil.

Leprosy is an infectious disease that may present different clinical forms depending on host immune response to Mycobacterium leprae. Mannose-binding lectin (MBL) is an acute phase protein associated with the pathophysiology of leprosy. Some studies have shown that there is a correlation between serum levels of MBL and polymorphisms in its gene associated with susceptibility per se and to different clinical forms. The aim of this study was to conduct a systematic review of publications in the literature that studied the association of MBL with leprosy. Databases were searched until December 2020 (PROSPERO: CRD42020158458), and additional searches were conducted scanning the reference lists of the articles. Two independent reviewers assessed the study quality using the Newcastle-Ottawa Quality Assessment Scale. Finally, 10 eligible articles were included in the study. The overall results indicated that both low MBL serum levels and polymorphisms in the structural or promoter region of its gene seem to be associated as protective factors against the development of severe forms. The results suggest that MBL may play a role in the clinical progression of leprosy.
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http://dx.doi.org/10.1016/j.meegid.2021.104945DOI Listing
May 2021

Potential role of microRNAs as biomarkers in human glioblastoma: a mini systematic review from 2015 to 2020.

Mol Biol Rep 2021 May 25;48(5):4647-4658. Epub 2021 May 25.

Laboratório de Biologia Molecular de Doenças Infecciosas, Departamento de Parasitologia, Instituto Aggeu Magalhães (IAM), Fundação Oswaldo Cruz (FIOCRUZ), 50670-420, Recife, Pernambuco, Brasil.

Glioblastoma (GBM) is the most common, aggressive and malignant type of glioma, with poor prognosis, despite advances in medical knowledge and technology. It's known that some microRNAs (miRNAs) can be dysregulated and associated with tumors. We aim to investigate miRNAs that may have a role as potential biomarkers in human glioblastoma. A search was performed using PubMed, LILACS and SCIELO databases to find papers from 2015 to 2020, related to human in vitro and ex vivo data. From 99 articles, 10 were eligible and 13 dysregulated miRNAs were found with description of regulation, target(s), pathway(s) and mechanism(s). The miRNAs of interest were found and seem to be involved in development and progression of glioblastoma and used as target therapies. Understanding the mechanisms in which those miRNAs are involved and their role in epigenetic pathways that lead to cancer, as well as their potential in clinical application, may improve GBM clinical outcome (CRD42020182706, 07/10/2020, retrospectively registered).
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http://dx.doi.org/10.1007/s11033-021-06423-9DOI Listing
May 2021

The 1G/1G+1G/2G Genotypes of rs1799750 Are Associated with Higher Levels of MMP-1 and Are Both Associated with Lipodystrophy in People Living with HIV on Antiretroviral Therapy.

AIDS Res Hum Retroviruses 2021 05 22;37(5):399-406. Epub 2021 Mar 22.

Faculty of Medical Sciences (FCM), University of Pernambuco (UPE), Recife, Brazil.

In HIV-infected patients, antiretroviral therapy (ART) is associated to adipose tissue redistribution known as lipodystrophy (LD). This study aimed at verifying the association between the polymorphism of the gene (rs1799750) (1G/2G) and the serum levels of matrix metalloproteinase 1 (MMP-1) with LD and its subtypes in people living with HIV on ART. This is a cross-secional study. LD was self-reported. The determination of the rs1799750 gene polymorphism was performed by real-time PCR, and the serum concentrations of MMP-1 were quantified by the enzyme-linked immunosorbent assay (ELISA) method. Of 404 participants, 204 (51%) were diagnosed with LD, of whom 89 (43%) had mixed lipodystrophy (ML), 72 (35%) had lipohypertrophy (LH), and 43 (22%) had lipoatrophy (LA). There was an association between the genotypes 1G/1G+1G/2G and higher serum levels of MMP-1 ( = .025). There was no association of (1G/2G) with LD. Other factors associated with LD were current CD4 ≤ 350 [odds ratio (OR) = 4.85, confidence interval (CI) = 1.78-47.99,  = .0033] and serum MMP-1 levels >6.81 (OR = 2.67, CI = 1.21-6.08,  = .0165). Factors associated with ML: current CD4 ≤ 350 (OR = 5.59, CI = 1.69-20.39,  = .006); with LH: number of antiretroviral regimens used: 2 (OR = 2.06, CI = 1.01-4.20,  = .0460) and 3+ (OR = 2.09, CI = 1.00-4.35,  = .0477), and current CD4 ≤ 350 (OR = 2.08, CI = 1.00-4.24,  = .0461); and with LA: current viral load >40 (OR = 2.52, CI = 1.03-5.91,  = .0372) and current use of zidovudine (OR = 2.97, CI = 1.32-6.54,  = .0074). Higher levels of MMP-1 were associated with genotypes 1G/2G+1G/1G and with LD. Other individual risk factors were independently associated with LD, and its subtypes, suggesting that the pathogenesis itself is differently manifested for each type of LD.
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http://dx.doi.org/10.1089/AID.2020.0237DOI Listing
May 2021

Multiple Introductions Followed by Ongoing Community Spread of SARS-CoV-2 at One of the Largest Metropolitan Areas of Northeast Brazil.

Viruses 2020 12 9;12(12). Epub 2020 Dec 9.

Departamento de Entomologia, Instituto Aggeu Magalhães (IAM)-Fundação Oswaldo Cruz-FIOCRUZ, Recife 50670-420, Brazil.

Multiple epicenters of the SARS-CoV-2 pandemic have emerged since the first pneumonia cases in Wuhan, China, such as Italy, USA, and Brazil. Brazil is the third-most affected country worldwide, but genomic sequences of SARS-CoV-2 strains are mostly restricted to states from the Southeast region. Pernambuco state, located in the Northeast region, is the sixth most affected Brazilian state, but very few genomic sequences from the strains circulating in this region are available. We sequenced 101 strains of SARS-CoV-2 from patients presenting Covid-19 symptoms that reside in Pernambuco. Phylogenetic reconstructions revealed that all genomes belong to the B lineage and most of the samples (88%) were classified as lineage B.1.1. We detected multiple viral introductions from abroad (likely from Europe) as well as six local B.1.1 clades composed by Pernambuco only strains. Local clades comprise sequences from the capital city (Recife) and other country-side cities, corroborating the community spread between different municipalities of the state. These findings demonstrate that different from Southeastern Brazilian states where the epidemics were majorly driven by one dominant lineage (B.1.1.28 or B.1.1.33), the early epidemic phase at the Pernambuco state was driven by multiple B.1.1 lineages seeded through both national and international traveling.
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http://dx.doi.org/10.3390/v12121414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763515PMC
December 2020

Influence of LGALS3 and PNPLA3 genes in non-alcoholic steatohepatitis (NASH) in patients undergone bariatric surgery.

Obes Res Clin Pract 2020 Jul - Aug;14(4):326-332. Epub 2020 Jul 18.

School of Medical Sciences, University of Pernambuco, Brazil; Institute of Liver and Transplant of Pernambuco, Brazil.

Aim: This study evaluated the genesPNPLA3 and LGALS3 in patients who have undergone bariatric surgery.

Methods: Individuals with NAFLD and NASH were evaluated, the DNA was extracted from total blood for genotyping of rs4644, rs4652 from LGALS3 and rs738409 from PNPLA3 genes, the total RNA was obtained from liver biopsy. For the detection of the molecular targets, real-time PCR through Taqman probes was used.

Results: From a total of 46 collected patients, of those 21 (456%) were included as NASH and 25 (544%) as steatosis group. This groups showed significant difference to aspartate aminotransferase (AST), alanine aminotransferase (ALT) and Glutamyl transpeptidase (GGT) (p = 0.0108, p = 0.0090 and p = 0.0044). Regarding to gene expression in studied groups, hepatic steatosis vs NASH, we observed a higher expression of the LGALS3 gene in NASH (p = 0.0273). In addition, patients with C allele in homozygous for rs4644 and rs4652 of LGALS3 gene had higher expression, in NASH group (p = 0.0500 and p = 0.0242, respectively), furthermore for rs4644 both alleles in homozygous showed higher expression (AA/CC vs AC) (p = 0.0500), when analyzed PNPLA3 rs738409, NASH patients with G allele in homozygous had higher expression (p = 0.0494).

Conclusions: Therefore, an increased expression of the LGALS3 gene in patients with NASH may be important in the etiopathogenesis of the disease, as well as the presence of rs4652 and rs4644 SNPs in the regulation of transcriptional levels of the gene in patients with NAFLD and NASH.
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http://dx.doi.org/10.1016/j.orcp.2020.07.004DOI Listing
July 2020

Association between interferon lambda 3 rs12979860 polymorphism and clinical outcome in dengue virus-infected children.

Int J Immunogenet 2020 Aug 17;47(4):351-358. Epub 2020 Feb 17.

Instituto de Ciências Biológicas, Universidade de Pernambuco, Recife, Brasil.

Single nucleotide polymorphisms (SNPs) in immune-related genes have been shown to play a role in driving the development of the severe phenotypes of dengue virus (DENV) infection. We assessed the association between IFNL3 gene SNP (rs12979860) and dengue clinical outcomes in children. Patients with dengue-related symptoms (aged 1-15 years) admitted at a public hospital in Northeast Brazil were invited to participate. The association between rs12979860 polymorphism and dengue classification and clinical signs and symptoms were analysed. A total of 206 DENV-infected children were included: 53.4% of the infections were classified as severe dengue. The T allele carriers had higher risk of developing severe dengue when compared to CC genotype carriers (OR: 1.81; 95% CI: 0.98-3.32 p = .054). The T allele carriers also showed longer fever episodes when compared to patients with the CC genotype (OR: 1.90; 95%CI: 1.07-3.38; p = .027). On the other hand, the ones carrying the CT/TT genotype had 70% lower chance of developing thrombocytopenia when compared to those with the CC genotype (OR: 0.30; 95%CI: 0.08-0.88; p = .042). Our findings demonstrated that the T allele carriers of the IFNL3 gene had higher risk of developing severe dengue, suggesting a link between IFN-λ expression and DENV immunopathogenesis.
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http://dx.doi.org/10.1111/iji.12477DOI Listing
August 2020

Higher levels of TNF and IL-4 cytokines and low miR-182 expression in visceral leishmaniasis-HIV co-infected patients.

Parasite Immunol 2020 04;42(4):e12701

Department of Parasitology, Instituto Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, Brazil.

Aims: The aim of the present study was to assess serum cytokine and miRNA expression in visceral leishmaniasis-HIV (VL-HIV) co-infection and HIV mono-infection.

Methods And Results: We analysed 113 serum samples from HIV patients in areas endemic for leishmaniasis. The diagnosis of VL was confirmed in 65 of these 113 samples. The VL-HIV and HIV groups presented significant differences regarding haemoglobin level (P < .0001), lymphocyte count (P = .0444), white blood cell count (P = .0108), weight loss (P = .0310), HIV load (P < .0001) and CD4+ T-lymphocytes count (P = .0003). Levels of IL-6 and IL-10, IFN-γ and IL-6, IFN-γ and IL-10, TNF and IL-2 were positively correlated in VL-HIV co-infection, indicating higher serum levels of TNF and IL-4 (P < .0001). In addition, miR-182 expression was found to be significantly higher in HIV (P = .009), miR-210 exhibited no statistically significant difference between groups, and nonexpression of miR-122 was found in both groups.

Conclusion: Together, TNF, IL-4 and miR-182 may represent circulatory biomarkers of VL-HIV co-infection.
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http://dx.doi.org/10.1111/pim.12701DOI Listing
April 2020

SLC11A1 (rs3731865) polymorphism and susceptibility to visceral leishmaniasis in HIV-coinfected patients from Northeastern Brazil.

Parasitol Res 2020 Feb 6;119(2):491-499. Epub 2020 Jan 6.

Department of Parasitology, Instituto Aggeu Magalhães, Fundação Oswaldo Cruz, Av. Prof. Moraes Rego s/n, Recife, Pernambuco, 50740-465, Brazil.

Following the emergence of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), the number of visceral leishmaniasis-HIV (VL-HIV) coinfections has increased worldwide, mainly in Brazil. The development of clinical forms of VL can be influenced by nutritional status, age, and host genetic factors, which are important variables determining susceptibility to disease. There are no studies with a candidate gene approach assayed directly in the VL-HIV-coinfected population. Herein, we determined and analyzed the associations of SLC11A1, LECT2, CCL1, CCL16, and IL4 genetic polymorphisms with susceptibility to VL-HIV coinfection in Northeastern Brazil. We analyzed 309 DNA samples extracted from the peripheral blood of HIV patients, and clinical and hematological data were collected from medical records. The diagnosis of VL was confirmed in 110 out of 309 patients; genotyping was carried out by TaqMan assays afterwards. Our results confirmed the association between the SLC11A1 polymorphism (rs3731865) and VL-HIV coinfection (p = 0.0206, OR 1.8126, 95% CI 1.1050-2.9727). In addition, the SLC11A1 genotype GG (p = 0.0050, OR 3.0395, 95% CI 1.4065-6.5789) and CD4+ T lymphocyte count (p = 0.0030, OR 0.9980, 95% CI 0.9970-0.9990) were associated with VL-HIV coinfection in a multivariate model. The polymorphism of the SLC11A1 gene (rs3731865) was associated with VL-HIV coinfection, suggesting a possible genetic mechanism involved in the susceptibility to VL in HIV patients. This finding can suggest new therapeutic targets and genetic markers for the VL-HIV-coinfected population.
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http://dx.doi.org/10.1007/s00436-019-06596-0DOI Listing
February 2020

Polymorphisms of and genes related to time in therapeutic range in patients with atrial fibrillation using warfarin.

Appl Clin Genet 2019 2;12:151-159. Epub 2019 Aug 2.

Pronto Socorro Cardiológico Professor Luiz Tavares - PROCAPE/UPE , Recife, Brazil.

Introduction: Warfarin continues to be the most widely used anticoagulant in clinical practice around the world for the prevention of thromboembolic events in patients with atrial fibrillation (AF). The evaluation of the quality of anticoagulation control, estimated by time in therapeutic range (TTR), is accepted as a good method to evaluate the quality of anticoagulation. The variability of TTR can be explained by the presence of variants of the and genes.

Methods: This study examined the association between polymorphisms of the  and  genes and control of oral anticoagulation, through TTR, in patients with AF. A cross-sectional study was conducted within a cohort follow-up. The study comprised of 317 patients with AF, using warfarin, who were followed up for one year. The genotyping of genes (rs1057910), (rs1799853) and (rs923231) was performed by PCR in real time, using TaqMan probes.

Results: Patients who had variant genotypes for the gene (rs1057910) presented higher TTR (TTR 81-100%) when compared to when compared to the <45% and 46-60% TTR groups (=0.005 and =0.002, respectively). Regarding (rs923231), patients who had the variant genotype for the (rs923231) gene also presented a higher TTR (TTR 81-100%), when when compared to the <45% and 46-60% TTR groups (=0.005 and =0.004, respectively). In a multivariate model, (rs923231) remained associated for comparisons with the TTR groups (<45% vs 81-100% groups, =0.01; and 46-60% vs 81-100% groups, =0.01).

Conclusion: The genotypes of the (AA) and -1639 (GG) genes were associated with the worst quality of anticoagulation control (TTR) in patients with AF using warfarin in the northeast of Brazil.
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http://dx.doi.org/10.2147/TACG.S197316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684853PMC
August 2019

Does physical exercise influence in the development of neuroeschistosomiasis?

Brain Res Bull 2019 10 1;152:311-322. Epub 2019 Aug 1.

Instituto Aggeu Magalhães - FIOCRUZ, Recife, Pernambuco, Brazil.

Neuroschistosomiasis is a severe form of presentation of schistosomiasis in which Schistosoma spp. affects the central nervous system. This is the first study performed to analyze whether there is any relationship between physical effort and the appearance of neuroschistosomiasis, through clinical, molecular and immunological evaluations. An experimental controlled study using 64 male Balb/c inbred mice divided into four groups according to presence or absence of S. mansoni infection and submitted to physical effort or resting was conducted. Thirteen weeks after exercise training, S. mansoni DNA was detected in the brain or spinal cord in about 30% of the infected animals moreover, only S. mansoni-positive samples showed positive labeling for S. mansoni antigens in the brain or spinal cord, with a striking reaction inside the microglia. However, the behavioral tests did not show any clinical symptoms of neuroschistosomiasis in animals submitted to physical effort or in resting. In animals with S. mansoni-positive DNA, immunohistochemical data revealed astrogliosis and microgliosis, elevated IL-10 levels and decreased TNF-α expression. This study demonstrated that isometric exercise does not promote neuroschistosomiasis, furthermore, ectopic forms of schistosomiasis in the central nervous system were largely asymptomatic and exhibited a Th2 immune response profile. More experimental studies are necessary in order to characterize the pathological process of experimental neuroschistosomiasis.
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http://dx.doi.org/10.1016/j.brainresbull.2019.07.029DOI Listing
October 2019

Expression of microRNAs (133b and 138) and Correlation with Echocardiographic Parameters in Patients with Alcoholic Cardiomyopathy.

Microrna 2020 ;9(2):112-120

Faculdade de Ciencias Medicas/ Universidade de Pernambuco - FCM/UPE, Recife, Pernambuco, Brazil.

Introduction: Alcoholic Cardiomyopathy (ACM) is a disease with a difficult diagnosis. The real mechanisms related to its pathophysiology are not fully understood.

Objective: The aims of this study were to investigate whether miR-133b and miR-138 could be associated with ACM.

Methods: Forty-four patients were included comprising 24 with ACM and 20 with cardiomyopathies of different etiologies (control group). Real-time PCR was performed to verify the relative expression among the studied groups. In the statistical analysis, the quantitative variables t-student Mann- Whitney and correlation of Pearson tests were carried out, while the qualitative variable comprised the chi-square test, with p<0.05 being considered statistically significant.

Results: There was no association between clinical and sociodemographic characteristics of the groups. The patients with ACM presented downregulation of miR-133b in comparison with control patients (p=0.004). On the other hand, for the miR-138, there was no association when the ACM group was compared with the control group. The presence of miR-133b among cases and controls was not correlated with any of the echocardiographic parameters. However, the increase in the expression of miR-138 was correlated with an increase in the ejection fraction (r=0.28, p=0.01) and the diameter of the left atrium (r=0.23, p=0.04) in patients with ACM.

Conclusion: The downregulation of miR-133b might be a marker for ACM and, in addition, miR- 138 could be used to correlate the increase in ejection fraction with and normalization of the diameter of the left atrium diameter in patients with this disease.
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http://dx.doi.org/10.2174/2211536608666190716151900DOI Listing
May 2021

Two sides of a coin: GG genotype of C7 provides protection against fibrosis severity while showing a higher risk for hepatocellular carcinoma in patients with hepatitis C.

Hum Immunol 2018 Sep 30;79(9):702-707. Epub 2018 Jun 30.

Institute of Biological Sciences/ICB-UPE, University of Pernambuco, Brazil.

The complement system (CS) is a key element of immunity against pathogens but also seems to influence other events, such as tumorigenesis and tissue repair. Complement component 7 (C7) is a key component of the lytic pathway of CS, leading to the formation of the membrane attack complex (MAC). This study aimed to investigate the existence of the association of a polymorphism in the C7 gene, rs1063499, with hepatic fibrosis and the occurrence of hepatocellular carcinoma (HCC) in patients with hepatitis C. We analyzed 456 samples from patients with chronic hepatitis C. Real-time PCR was used for allelic discrimination. Patients were classified by their METAVIR score as F1 (n = 100), F2 (n = 83), F3 (n = 101) or F4 (n = 66); 106 patients were diagnosed with HCC. Patients carrying the G/G genotype of C7 had a lower chance of developing severe fibrosis in the recessive model (p = 0.042; OR: 0.65 95% CI 0.41-1.02). However, the G/G genotype frequency was higher in patients with HCC (P = 0.01; OR: 2.07 95% CI 1.20-3.53) and in those with larger tumors (p = 0.04). The G/G C7 genotype seems to be a protective factor against advanced fibrosis; however, it was associated with a higher risk of HCC and the occurrence of larger hepatic nodules, suggesting the involvement of C7 in the physiopathogenesis of HCC and fibrosis in patients with hepatitis C virus (HCV).
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http://dx.doi.org/10.1016/j.humimm.2018.06.009DOI Listing
September 2018

Association of the Polymorphism (Val16Ala) and SOD Activity with Vaso-occlusive Crisis and Acute Splenic Sequestration in Children with Sickle Cell Anemia.

Mediterr J Hematol Infect Dis 2018 21;10(1):e2018012. Epub 2018 Feb 21.

Biological Science Institute, University of Pernambuco Pernambuco, Brazil.

The SOD2 polymorphism Val16Ala T→C influences the antioxidative response. This study investigated the association of the SOD2 polymorphism and superoxide dismutase (SOD) activity with the vaso-occlusive crisis (VOC) and acute splenic sequestration (ASS) in children with sickle cell anemia (SCA). One hundred ninety-five children with SCA aged 1-9 years old were analyzed. The TC and CC genotypes were associated with lower SOD activity compared with the TT genotype (p=0.0321; p=0.0253, respectively). Furthermore, TC and CC were more frequent in patients with VOC or ASS (p=0.0285; p=0.0090, respectively). These results suggest that the SOD2 polymorphism associated with low SOD activity could be a susceptibility factor for the occurrence of VOC and ASS.
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http://dx.doi.org/10.4084/MJHID.2018.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841937PMC
February 2018

Cognitive Dysfunction and Single Nucleotide Polymorphisms in Hepatitis C Virus-Infected Persons: A Systematic Review.

Viral Immunol 2017 12 10;30(10):703-707. Epub 2017 Oct 10.

6 Hospital Universitário Oswaldo Cruz; Medical Sciences College, Universidade de Pernambuco (UPE) , Recife, PE, Brazil .

The aim of this study was to realize a systematic review to identify data reported in the literature involving people infected by hepatitis C virus (HCV) with cognitive dysfunctions and single nucleotide polymorphisms (SNPs). The research was realized in six databases and the selection of studies was performed in two stages. Initially, we searched indexed articles from the following electronic databases: SciELO, MEDLINE, PubMed, HighWire, LILACS, and ScienceDirect. Then the articles were completely read and those that did not meet the eligibility criteria were excluded. Therefore, 5,669 articles were obtained and, of these, 25 were selected. Finally, one article involving people with HCV and cognitive impairment was included in the review. The frequency of the APOE-ɛ4 allele in people with HCV and mild liver disease was significantly lower in those with work memory impairment (p = 0.003) and attention (p = 0.008). This situation differs from other studies that showed an association between ɛ4 allele high frequency and cognitive decline. Thus, studies with larger samples involving people with HCV, cognitive alterations, and SNPs are necessary, in view of the lack of this theme in the literature and the divergences in the findings.
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http://dx.doi.org/10.1089/vim.2017.0084DOI Listing
December 2017

Combined genotypes of the MBL2 gene related to low mannose-binding lectin levels are associated with vaso-occlusive events in children with sickle cell anemia.

Genet Mol Biol 2017 Jul-Sep;40(3):600-603. Epub 2017 Aug 21.

Instituto de Ciências Biológicas/Faculdade de Ciências Médicas, Universidade de Pernambuco, Recife, PE, Brazil.

Sickle cell anemia (SCA) presents heterogenous clinical manifestations that cannot be explained solely by alterations to hemoglobin (Hb); other components such as endothelial adhesion, thrombosis and inflammation may be involved. The mannose-binding lectin (MBL) has an important role in innate immunity and inflammatory diseases. In this report, we describe an association between MBL2 polymorphism related to low production of serum MBL and the frequency of vasoocclusive events (FVOE) in children ≤ 5 years old with SCA (p = 0.0229; OR 5.55; CI 1.11-27.66). Further studies are needed to explore the role of low MBL2 in the pathophysiology of vasoocclusive events in SCA.
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http://dx.doi.org/10.1590/1678-4685-GMB-2016-0161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5596363PMC
August 2017

Association of rs1285933 single nucleotide polymorphism in CLEC5A gene with dengue severity and its functional effects.

Hum Immunol 2017 Oct 29;78(10):649-656. Epub 2017 Jul 29.

Laboratório de Hanseníase, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, RJ, Brazil. Electronic address:

Outbreaks of the Zika, dengue, and chikungunya viruses, especially in the Americas, pose a global threat due to their rapid spread and difficulty controlling the vector. Extreme phenotypes are often observed, from asymptomatic to severe clinical manifestations, which are well-studied in dengue. Host variations are also important contributors to disease outcomes, and many case-control studies have associated single nucleotide polymorphisms (SNPs) with severe dengue. Here, we found that the TC genotype and T-carriers for SNP rs1285933 in the C-type lectin superfamily member 5 (CLEC5A) gene was associated with severe dengue in a Northern Brazilian population (OR=2.75 and p-value=0.01, OR=2.11 and p-value=0.04, respectively). We also tested the functional effect of the CLEC5A protein and found that it is upregulated on the surface of human monocytes after in vitro dengue infection. CLEC5A was correlated with viral load inside the monocytes (Spearman r=0.55, p=0.008) and TNF production in culture supernatants (Spearman r=0.72, p=0.03). Analysis of mRNA in blood samples from DENV4-infected patients exhibiting mild symptoms showed that CLEC5A mRNA expression is correlated with TNF (r=0.67, p=0.0001) and other immune mediators. Monocytes from rs1285933 TT/TC individuals showed lower CLEC5A expression compared to CC genotypes. However, in these cells, CLEC5A was not correlated with TNF production. In summary, we confirmed that CLEC5A is genetically associated with dengue severity outcome, playing a central role during the immune response triggered by a dengue viral infection, and rs1285933 is a relevant SNP that is able to regulate signaling pathways after interactions between the dengue virus and CLEC5A receptors.
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http://dx.doi.org/10.1016/j.humimm.2017.07.013DOI Listing
October 2017

Single Nucleotide Polymorphisms at +191 and +292 of Galectin-3 Gene (LGALS3) Related to Lower GAL-3 Serum Levels Are Associated with Frequent Respiratory Tract Infection and Vaso-Occlusive Crisis in Children with Sickle Cell Anemia.

PLoS One 2016 7;11(9):e0162297. Epub 2016 Sep 7.

Programa de Doutorado da Rede Nordeste de Biotecnologia, Recife, Brasil.

Introduction: Patients with sickle cell anemia (SCA) may present chronic hemolytic anemia, vaso-occlusion and respiratory tract infection (RTI) episodes. Galectin-3 (GAL-3) is a multifunctional protein involved in inflammation, apoptosis, adhesion and resistance to reactive oxygen species. Studies point to a dual role for GAL-3 as both a circulation damage-associated molecular pattern and a cell membrane associated pattern recognition receptor.

Objective: To investigate associations between the SNPs of GAL-3 gene (LGALS3) and serum levels with RTI and vaso-occlusive crisis (VOC) in children with SCA.

Materials And Methods: SNPs +191 and +292 in LGALS3 were studied using the TaqMan real-time PCR system; GAL-3 serum levels were measured by ELISA. The study included 79 children with SCA ranging from 2 to 12 years old.

Results: GAL-3 serum levels were associated with LGALS3 +191 and +292 genotypes (p <0.0001; p = 0.0169, respectively). LGALS3 +191, AA genotype was associated with low and CC with higher levels of GAL-3. For LGALS3 +292, the CC genotype was associated with lower GAL-3 and AA with higher levels. Patients with Frequency of RTI (FRTI) ≥1 presented higher frequency of +191AA (p = 0.0263) and +292AC/CC genotypes (p = 0.0320). SNP +292 was associated with Frequency of VOC (FVOC) (p = 0.0347), whereas no association was shown with SNP +191 and FVOC. However, CA/AC and AA/CC genotypes with lower GAL-3 levels showed a higher frequency in patients with FRTI ≥1 (p = 0.0170; p = 0.0138, respectively). Also, patients with FVOC ≥1 presented association with CA/AC (p = 0.0228). LGALS3 +191 and +292 combined genotypes related to low (p = 0.0263) and intermediate expression (p = 0.0245) were associated with FRTI ≥1. Lower GAL-3 serum levels were associated with FRTI ≥1 (p = 0.0426) and FVOC ≥1 (p = 0.0012).

Conclusion: Variation of GAL-3 serum levels related to SNPs at +191 and +292 may constitute a susceptibility factor for RTI and VOC frequency.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0162297PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5014331PMC
August 2017

Mannose-binding lectin gene (MBL2) polymorphisms related to the mannose-binding lectin low levels are associated to dengue disease severity.

Hum Immunol 2016 Jul 11;77(7):571-5. Epub 2016 May 11.

Instituto de Ciências Biológicas, Universidade de Pernambuco (UPE), Brazil. Electronic address:

Dengue is the main arbovirosis in the tropical and subtropical areas of the world. The majority of infected individuals present an asymptomatic outcome while others progress to dengue fever (DF) or dengue haemorrhagic fever (DHF). Dengue infection evolution to severe outcomes is in part, related to innate immunity response. The MBL2 gene encodes for a pathogen recognition pattern molecule, the mannose-binding lectin (MBL). Variant alleles at promoter and structural regions of the MBL2 are related to serum MBL levels and function. Due to the important inflammatory modulation role of MBL, MBL2 polymorphisms could influence dengue progression. Therefore, this study investigated associations of MBL2 polymorphisms and serum MBL levels in patients with dengue. Genotyping of promoter and structural regions of MBL2 was performed by real-time PCR using Taqman® probes in 161 patients presenting DF or DHF outcome. For the serum MBL determination a commercial ELISA kit was used. The variant OO genotype and O allele were associated with DHF (p=0.008 and p=0.009 respectively). Haplotypes correlated to MBL low levels were associated with DHF (p=0.04). Our results support the hypothesis that patients carrying genotypes or haplotypes of low production of MBL would be more susceptible to DHF.
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http://dx.doi.org/10.1016/j.humimm.2016.05.006DOI Listing
July 2016

TNF-α and IL-10 polymorphisms increase the risk to hepatocellular carcinoma in HCV infected individuals.

J Med Virol 2016 09 21;88(9):1587-95. Epub 2016 Mar 21.

Setor de Virologia do Laboratório de Imunopatologia Keizo-Asami (LIKA), Universidade Federal de Pernambuco (UFPE), Brazil.

Hepatitis C virus (HCV) is the major cause of hepatocellular carcinoma (HCC). The risk to develop HCC increases with the severity of liver inflammation and hepatic fibrosis. It is believed that a balance between the releases of pro- and anti-inflammatory cytokines will determine the clinical course of HCV and the risk to develop HCC. The inteleukin-10 (IL-10) and the tumor necrosis factor alpha (TNF-α) play key roles in the Th1 and Th2 balance during the inflammatory response against HCV. The aim of the present study was to investigate the association between polymorphisms in TNF-α -308 G>A (rs1800629), IL-10 -1082 G>A (rs1800896) and -819/-592 (rs1800871/rs1800872) with HCC risk in individuals with HCV. The present study evaluated 388 chronic HCV patients. Polymorphisms were determined by real-time PCR. Diplotypes associated with low IL-10 production and the TNF-α GG genotype were significantly associated with HCC occurrence after multivariate logistic regression analysis (P = 0.027 and P = 0.029, respectively). Additionally, the IL-10 -819 (-592) TT (AA) genotype was significantly associated with multiple nodules and HCC severity according to BCLC staging (P = 0.044 and P = 0.025, respectively). Patients carrying low production haplotypes of IL-10 and the TNF-α GG genotype have higher risk to develop HCC. J. Med. Virol. 88:1587-1595, 2016. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/jmv.24501DOI Listing
September 2016

Association of a variant in the regulatory region of NADPH oxidase 4 gene and metabolic syndrome in patients with chronic hepatitis C.

Eur J Med Res 2015 Mar 28;20:45. Epub 2015 Mar 28.

Department of Gastroenterology (LIM-07), School of Medicine, University of São Paulo, Av. Dr Arnaldo, 455, 3° Andar, #3115, Cep.: 1246903, São Paulo, Brazil.

Background: Given the important contribution of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system to the generation of reactive oxygen species induced by hepatitis C virus (HCV), we investigated two single nucleotide polymorphisms (SNPs) in the putative regulatory region of the genes encoding NADPH oxidase 4 catalytic subunit (NOX4) and its regulatory subunit p22phox (CYBA) and their relation with metabolic and histological variables in patients with HCV.

Methods: One hundred seventy eight naïve HCV patients (49.3% male; 65% HCV genotype 1) with positive HCV RNA were genotyped using specific primers and fluorescent-labeled probes for SNPs rs3017887 in NOX4 and -675 T → A in CYBA.

Results: No association was found between the genotype frequencies of NOX4 and CYBA SNPs and inflammation scores or fibrosis stages in the overall population. The presence of the CA + AA genotypes of the NOX4 SNP was nominally associated with a lower alanine aminotransferase (ALT) concentration in the male population (CA + AA = 72.23 ± 6.34 U/L versus CC = 100.22 ± 9.85; mean ± SEM; P = 0.05). The TT genotype of the CYBA SNP was also nominally associated with a lower ALT concentration in the male population (TT = 84.01 ± 6.77 U/L versus TA + AA = 109.67 ± 18.37 U/L; mean ± SEM; P = 0.047). The minor A-allele of the NOX4 SNP was inversely associated with the frequency of metabolic syndrome (MS) in the male population (odds ratio (OR): 0.15; 95% confidence interval (CI): 0.03 to 0.79; P = 0.025).

Conclusions: The results suggest that the evaluated NOX4 and CYBA SNPs are not direct genetic determinants of fibrosis in HCV patients, but nevertheless NOX4 rs3017887 SNP could indirectly influence fibrosis susceptibility due to its inverse association with MS in male patients.
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http://dx.doi.org/10.1186/s40001-015-0136-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4383049PMC
March 2015

Low IL10 serum levels as key factor for predicting the sustained virological response to IFNα/ribavirin in Brazilian patients with HCV carrying IL28B CT/TT genotype.

Hum Immunol 2014 Aug 30;75(8):895-900. Epub 2014 Jun 30.

Liver Institute of Pernambuco, Recife, PE 50100-130, Brazil; University of Pernambuco, Recife, PE 50100-130, Brazil.

Propose: IL28B polymorphisms rs12979860 CC genotype was associated to protection of HCV infection and sustained virological response (SVR) in HCV infected patients treated with pegIFNα/ribavirin (IFNα/RIB), however, this polymorphism frequency varies depending on genetic components. Studies with larger number of Brazilian individuals, determining IL28B polymorphisms is lacking. Regarding to treatment response, the levels of IL10 seem to influence response to IFNα/RIB therapy. Thus, the IL28B polymorphism frequency was investigated in health controls and infected HCV patients, as well as, in patients who reach SVR vs Non-SVR. Also, to gain insight into the interplay between IL28B genotypes, IL10 levels and therapy response, a subgroup of genotyped HCV patients SVR and Non-SVR were analyzed regarding the IL10 production.

Methods: It was enrolled 487 HCV infected patients and 234 healthy individuals. Patients with response to IFNα/RIB were classified as SVR (n = 81) and Non-SVR (n = 123). TAQMAN probes were used for genotyping the SNP rs12979860, resulting in CC, CT or TT genotypes. In one hundred one patients, the levels IL10 were measured at week 4 of IFNα/RIB.

Results: CC genotype was associated to SVR (p = 0.029) and its frequency was higher in healthy individuals vs patients (p = 0.02). Patients carrying CT/TT with IL10<10 pg/mL, had a chance of 2.72 to achieve SVR in multivariate model (p = 0.043).

Conclusion: CC genotype was associated to SVR and protection to HCV infection. Moreover, IL28B genotyping and IL10 serum levels could be further explored as a useful algorithm for identify the CT/TT SVR patients.
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http://dx.doi.org/10.1016/j.humimm.2014.06.017DOI Listing
August 2014

Myeloperoxidase gene polymorphism predicts fibrosis severity in women with hepatitis C.

Hum Immunol 2014 Aug 2;75(8):766-70. Epub 2014 Jun 2.

Instituto de Ciências Biológicas, Universidade de Pernambuco, Pernambuco, Brazil.

Oxidative stress plays an important role on liver fibrosis progression in the course of hepatitis C virus (HCV) infection. Myeloperoxidase (MPO) is an enzyme released by neutrophils and macrophages, responsible for generating hypochlorous acid and reactive oxygen species (ROS) that may lead to liver injury in HCV infection. On the other hand, antioxidant enzymes such as manganese superoxide dismutase (SOD) controls ROS-mediated damage. The aim of the present study was to investigate the influence of MPO G-463A and SOD2 Ala16Val polymorphisms in the severity of liver fibrosis in individuals with chronic HCV infection. The present study included 270 patients with chronic HCV recruited from the Gastrohepatology Service of the Oswaldo Cruz University Hospital/Liver Institute of Pernambuco (Recife, Northeastern Brazil). All patients underwent liver biopsy, which was classified according METAVIR score. The SNPs were determined by real-time PCR. After multivariate analysis adjustment, the GG genotype of MPO and the presence of metabolic syndrome were independently associated with fibrosis severity in women (P = 0.025 OR 2.25 CI 1.10-4.59 and P = 0.032 OR 2.32 CI 1.07-5.01, respectively). The presence of the GG genotype seems to be a risk factor for fibrosis severity in women with HCV.
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http://dx.doi.org/10.1016/j.humimm.2014.05.008DOI Listing
August 2014

Plasma myeloperoxidase levels correlate with hepatocellular carcinoma in chronic hepatitis C.

Hum Immunol 2012 Nov 15;73(11):1127-31. Epub 2012 Sep 15.

Institute of Biological Science, University of Pernambuco, Recife, Pernambuco, Brazil.

Myeloperoxidase (MPO) is an enzyme responsible for generating hypochlorous acid and reactive oxidants that may lead to liver injury and cancer in hepatitis C (HCV) infection. MPO expression level is regulated by a polymorphism in the promoter region -463 of MPO gene. In the current study, MPO plasma levels and the G-463A MPO polymorphism were determined in 158 chronically HCV infected patients with and without hepatocellular carcinoma (HCC). MPO plasma levels were determined using a commercially ELISA kit. The G-463A MPO polymorphism was accessed by real time PCR using TaqMan probes. The MPO plasma levels of patients with HCV-HCC were higher in comparison to patients with chronic hepatitis or with those patients with severe fibrosis (p=0.01 and p=0.04, respectively). The MPO G-463A polymorphism was not associated with HCV outcome. These findings suggest MPO levels monitoring may be a potential biological marker to HCC screening in patients with HCV.
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http://dx.doi.org/10.1016/j.humimm.2012.07.322DOI Listing
November 2012

Mannose-binding lectin serum levels in patients with leprosy are influenced by age and MBL2 genotypes.

Int J Infect Dis 2011 Aug 2;15(8):e551-7. Epub 2011 Jun 2.

Faculdade de Ciências Medicas, Instituto de Ciências Biológicas, Universidade de Pernambuco, Rua Arnobio Marques 282, CEP 50100-130, Santo Amaro, Recife PE, Brazil.

Background: Mannose-binding lectin (MBL) activates the complement system promoting opsonophagocytosis, which could represent an advantage for Mycobacterium leprae, an intracellular pathogen. Therefore, a single nucleotide polymorphism (SNP) in the MBL2 gene associated with low levels of MBL could confer protection against the development of leprosy disease.

Methods: In this study, we investigated SNPs of the MBL2 gene and MBL levels in 228 Brazilian leprosy patients and 232 controls.

Results: There were no differences in the frequencies of variant genotypes and haplotypes of MBL2 between patients and controls, or between the different clinical forms of leprosy. In the group of patients with a genotype for high expression of MBL2, those aged>40 years had decreased MBL levels compared to patients aged ≤ 40 years (p = 0.037).

Conclusion: Our results demonstrate that age could influence the phenotype of MBL2, but no evidence was found for an association of MBL2 polymorphism with susceptibility to leprosy or its clinical forms.
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http://dx.doi.org/10.1016/j.ijid.2011.04.008DOI Listing
August 2011

Association of hepatitis C virus infection and liver fibrosis severity with the variants alleles of MBL2 gene in a Brazilian population.

Hum Immunol 2010 Sep 1;71(9):883-7. Epub 2010 Jun 1.

Postgraduate Program RENORBIO, Brazil; Institute of Biological Sciences, University of Pernambuco, Recife, Brazil.

Mannose binding lectin (MBL) is a molecule of the innate immunity, which activates the complement system and modulates inflammation. We investigated the association of the polymorphisms in the exon 1 and promoter region of the MBL gene (MBL2) with the susceptibility to hepatitis C virus (HCV) infection and the degree of liver fibrosis in Brazilian patients chronically infected with HCV. The study was performed in 232 healthy control subjects and 186 patients, 157 of whom underwent liver biopsy after histopathology analysis and classification of fibrosis according to Metavir score. Exon 1 was genotyped by melting temperature assay and the promoter region by Taqman real-time polymerase chain reacation. The frequency of genotypes related to low production of MBL was higher in patients with HCV than in controls (p(c) = 0.0001, odds ratio = 3.52; confidence interval = 1.86-6.71). In addition, the frequency of variant haplotype, HYO was higher in patients with the severe fibrosis stage F4 (10.7%) than in patients with the mild/moderate fibrosis stage F1/F2 (3.4%), when compared with the HYA haplotype (p(c) = 0.04, odds ratio = 5.25, confidence interval = 1.11-23.62). We conclude that MBL variant alleles expressing low levels of MBL are associated with the susceptibility to HCV infection and that the inheritance of HYO haplotype could be associated with fibrosis severity.
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http://dx.doi.org/10.1016/j.humimm.2010.05.021DOI Listing
September 2010

Association of polymorphisms in the first exon of mannose binding lectin gene (MBL2) in Brazilian patients with HCV infection.

Clin Immunol 2007 Jul 21;124(1):13-7. Epub 2007 May 21.

Department of Reproductive and Developmental Sciences, University of Trieste, Trieste, Italy.

In our study we investigated the role of the polymorphisms in the first exon of MBL2 gene in the susceptibility to HCV infection and disease progression in a Northeastern Brazilian population. One hundred and eleven patients seen at the Gastroenterology Service of the Oswaldo Cruz Hospital of the University of Pernambuco were included in this study. A total of 165 unexposed, uninfected individuals matched for place of origin were employed as healthy controls. MBL2 genotyping was performed by using a melting temperature assay. The 0 allele was significantly more frequent in the HCV positive group than the healthy controls (34% vs. 20%, p<0.01, respectively) and was associated to an increased risk of HCV-1 infection (O.R.=2.1; C.I. 1.41-3.19). Also genotypes frequencies were significantly different in HCV positive subjects when compared to healthy controls with the 00 and A0 genotypes being significantly overrepresented in HCV infected subject (15% and 37%, respectively) as compared to healthy subjects (6% and 27%, respectively, p<0.01 ) Allele and genotypes frequencies were also evaluated in HCV infected subjects according to their response to pegylated-INFalpha/riboviron therapy. There was a trend for HCV positive responders vs. non-responders to be 0 allele positive and a similar trend was observed for the MBL2 A0 and 00 genotypes, but neither of these reached statistical significance. Our findings indicate that MBL might represent an important antiviral molecule having a protective role in the first stages of HCV infection, as shown by the increased frequency of wild-type alleles in control population as compared to the infected group.
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http://dx.doi.org/10.1016/j.clim.2007.04.006DOI Listing
July 2007
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