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1.
Rev Soc Bras Med Trop ; 54: e01452020, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33338108

RESUMO

INTRODUCTION: We evaluated the association between genetic polymorphisms in exon 1 (A/O alleles) and promoter regions at positions -550 (H/L variant, rs11003125) and -221 (X/Y variant, rs7096206) MBL2 and periportal fibrosis regression. METHODS: This was a retrospective cohort study involving 114 Brazilians infected with Schistosoma mansoni, who were subjected to follow-up for three years after specific treatment for schistosomiasis to estimate the probability of periportal fibrosis regression. RESULTS: A risk association was observed between polymorphism at the exon 1 MBL2 and periportal fibrosis regression. CONCLUSIONS: This study suggests that the polymorphism of exon 1 MBL2 may potentially be used to predict periportal fibrosis regression in this population.


Assuntos
Lectina de Ligação a Manose , Esquistossomose , Animais , Brasil , Éxons/genética , Predisposição Genética para Doença , Genótipo , Humanos , Cirrose Hepática/genética , Lectina de Ligação a Manose/genética , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Estudos Retrospectivos , Esquistossomose/genética
2.
Infect Genet Evol ; 84: 104498, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32771700

RESUMO

New coronavirus SARS-CoV-2 is capable to infect humans and cause a novel disease COVID-19. Aiming to understand a host genetic component of COVID-19, we focused on variants in genes encoding proteases and genes involved in innate immunity that could be important for susceptibility and resistance to SARS-CoV-2 infection. Analysis of sequence data of coding regions of FURIN, PLG, PRSS1, TMPRSS11a, MBL2 and OAS1 genes in 143 unrelated individuals from Serbian population identified 22 variants with potential functional effect. In silico analyses (PolyPhen-2, SIFT, MutPred2 and Swiss-Pdb Viewer) predicted that 10 variants could impact the structure and/or function of proteins. These protein-altering variants (p.Gly146Ser in FURIN; p.Arg261His and p.Ala494Val in PLG; p.Asn54Lys in PRSS1; p.Arg52Cys, p.Gly54Asp and p.Gly57Glu in MBL2; p.Arg47Gln, p.Ile99Val and p.Arg130His in OAS1) may have predictive value for inter-individual differences in the response to the SARS-CoV-2 infection. Next, we performed comparative population analysis for the same variants using extracted data from the 1000 Genomes project. Population genetic variability was assessed using delta MAF and Fst statistics. Our study pointed to 7 variants in PLG, TMPRSS11a, MBL2 and OAS1 genes with noticeable divergence in allelic frequencies between populations worldwide. Three of them, all in MBL2 gene, were predicted to be damaging, making them the most promising population-specific markers related to SARS-CoV-2 infection. Comparing allelic frequencies between Serbian and other populations, we found that the highest level of genetic divergence related to selected loci was observed with African, followed by East Asian, Central and South American and South Asian populations. When compared with European populations, the highest divergence was observed with Italian population. In conclusion, we identified 4 variants in genes encoding proteases (FURIN, PLG and PRSS1) and 6 in genes involved in the innate immunity (MBL2 and OAS1) that might be relevant for the host response to SARS-CoV-2 infection.


Assuntos
Infecções por Coronavirus/genética , Resistência à Doença/genética , Predisposição Genética para Doença , Interações Hospedeiro-Patógeno/genética , Metagenômica , Peptidil Dipeptidase A/genética , Pneumonia Viral/genética , Glicoproteína da Espícula de Coronavírus/genética , Alelos , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Proteínas do Olho/genética , Proteínas do Olho/imunologia , Furina/genética , Furina/imunologia , Frequência do Gene , Variação Genética , Genoma Humano , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata , Lectina de Ligação a Manose/genética , Lectina de Ligação a Manose/imunologia , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/imunologia , Pandemias , Peptidil Dipeptidase A/imunologia , Plasminogênio/genética , Plasminogênio/imunologia , Pneumonia Viral/imunologia , Ligação Proteica , Glicoproteína da Espícula de Coronavírus/imunologia , Tripsina/genética , Tripsina/imunologia
3.
Infect Dis Poverty ; 9(1): 46, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32349793

RESUMO

BACKGROUND: Immune- and inflammation-related genes (IIRGs) play an important role in the pathogenesis of tuberculosis (TB). However, the relationship between IIRG polymorphisms and TB risk remains unknown. In this study, the gene polymorphisms and their association with tuberculosis were determined in a Chinese population. METHODS: We performed a case-control study involving 1016 patients with TB and 507 healthy controls of Han Chinese origin. Sixty-four single-nucleotide polymorphisms (SNPs) belonging to 18 IIRGs were genotyped by the PCR-MassArray assay, and the obtained data was analyzed with χ2-test, Bonferroni correction, and unconditional logistic regression analysis. RESULTS: We observed significant differences in the allele frequency of LTA rs2229094*C (P = 0.015), MBL2 rs2099902*C (P = 0.001), MBL2 rs930507*G (P = 0.004), MBL2 rs10824793*G (P = 0.004), and IL12RB1 rs2305740*G (P = 0.040) between the TB and healthy groups. Increased TB risk was identified in the rs930507 G/G genotype (Padjusted = 0.027) under a codominant genetic model as well as in the rs2099902 (C/T + C/C) vs T/T genotype (Padjusted = 0.020), rs930507 (C/G + G/G) vs C/C genotype (Padjusted = 0.027), and rs10824793 (G/A + G/G) vs A/A genotype (Padjusted = 0.017) under a dominant genetic model after Bonferroni correction in the analysis of the overall TB group rather than the TB subgroups. Furthermore, the rs10824793_rs7916582*GT and rs10824793_rs7916582*GC haplotypes were significantly associated with increased TB risk (P = 0.001, odds ratio [OR] = 1.421, 95% confidence interval [CI]: 1.152-1.753; and P = 0.018, OR = 1.364, 95% CI: 1.055-1.765, respectively). Moreover, the rs10824793_rs7916582*AT/AT or rs10824793_rs7916582*GT/GT diplotype showed a protective (P = 0.003, OR = 0.530, 95% CI: 0.349-0.805) or harmful (P = 0.009, OR = 1.396, 95% CI: 1.087-1.793) effect against the development of TB. CONCLUSIONS: This study indicated that MBL2 polymorphisms, haplotypes, and diplotypes were associated with TB susceptibility in the Han Chinese population. Additionally, larger sample size studies are needed to further confirm these findings in the future.


Assuntos
Lectina de Ligação a Manose/genética , Polimorfismo de Nucleotídeo Único , Tuberculose/genética , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China , Feminino , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
J Clin Neurosci ; 78: 264-268, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32279906

RESUMO

The aim of this study to investigate the genetic polymorphisms in macrophage inhibitory factor (MIF) and mannose-binding lectin 2 (MBL2) gene in schizophrenia (SCZ) or bipolar disorder (BD) patients with attempted suicide by comparing with a non-attempted SCZ or BD patients and healthy controls. A sample of 108 patients with SCZ, 100 patients with BD and 100 healthy volunteers were included in the study. SCID-I was used to confirm the diagnosis according to DSM-IV-TR criteria. The patients were evaluated by data forms that included sociodemographic, suicidal behavior and symptom severity information. PCR-RFLP was used to determine MIF and MBL2 gene polymorphisms from DNA material. Our results demonstrated that the distributions of MBL2 genotype (AA, AB, BB), combined genotype (AA, AB/BB) and the allele frequencies (A, B) of attempted suicide patients in SCZ were significantly different from the non-attempted SCZ patients. The distributions of the MBL2 genotype of attempted suicide patients in SCZ were significantly different from the control group. The distributions of MIF genotype (GG, GC, CC), combined genotype (GG, GC/CC) and the allele frequencies (G, C) of attempted suicide patients in BD were significantly different from the non-attempted BD patients or control group. In summary MBL2 gene polymorphism may be associated with attempted suicide in SCZ and MIF gene polymorphism might be associated with attempted suicide in BD. However, further studies with other gene variants in different ethnic populations are needed to address the exact role of these polymorphisms in SCZ or BD.


Assuntos
Transtorno Bipolar/genética , Oxirredutases Intramoleculares/genética , Fatores Inibidores da Migração de Macrófagos/genética , Lectina de Ligação a Manose/genética , Polimorfismo Genético/genética , Esquizofrenia/genética , Tentativa de Suicídio , Adulto , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Tentativa de Suicídio/psicologia
5.
Sci Rep ; 10(1): 6079, 2020 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-32269261

RESUMO

The genetic variants of Mannose-Binding Lectin, a vital component of innate immunity have been studied with acute/recurrent vaginal infections ((R)VVI) and presented inconclusive findings. Therefore, a systematic review and meta-analysis of published data were conducted to assess the possible role of these variations in (R)VVI. A comprehensive search was made using PubMed, Web of Science and Google scholar till June 18, 2019. A total of 12 studies met the specified criteria and were included in the analysis. Different comparisons were made on the basis of the outcome of interest that resulted in the filtering of studies for the pooled analysis to find an association using the standard genetic models. Odds ratio (OR) with 95% confidence interval (CI) was chosen as the effect measure for the data synthesis. The trim and fill technique was applied to adjust the publication bias. The meta-analysis revealed the significant association (p < 0.05) of rs1800450 polymorphism with RVVI risk (OR ≥ 3.5) in all the genetic models. The subgroup analysis identified the same association in Caucasian and Mixed ethnicity. Quantitative synthesis based on RVVC showed>3.5 fold risk of disease development accredited to rs1800450. A combined evaluation of Exon1 variants showed no association with (R)VVI. This meta-analysis suggests rs1800450 polymorphism as a genetic predisposing factor for RVVI, but to reinforce, further studies with a larger sample size are warranted.


Assuntos
Lectina de Ligação a Manose/genética , Polimorfismo de Nucleotídeo Único , Vulvovaginite/genética , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva , Vulvovaginite/patologia
6.
Sci Rep ; 10(1): 3693, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111865

RESUMO

Cardiovascular (CV) morbidity is the major cause of death in patients with Systemic Lupus Erythematosus (SLE). Previous studies on mannose-binding lectin (MBL) gene polymorphisms in SLE patients suggest that low levels of complement MBL are associated with cardiovascular disease (CVD). However, as large studies on MBL deficiency based on resulting MBL plasma concentrations are lacking, the aim of our study was to analyze the association of MBL concentrations with CVD in SLE patients. Plasma MBL levels SLE patients included in the Swiss SLE Cohort Study were quantified by ELISA. Five different CV organ manifestations were documented. Of 373 included patients (85.5% female) 62 patients had at least one CV manifestation. Patients with MBL deficiency (levels below 500 ng/ml or 1000 ng/ml) had no significantly increased frequency of CVD (19.4% vs. 15.2%, P = 0.3 or 17.7% vs. 15.7%, P = 0.7). After adjustment for traditional CV risk factors, MBL levels and positive antiphospholipid serology (APL+) a significant association of CVD with age, hypertension, disease duration and APL+ was demonstrated. In our study of a large cohort of patients with SLE, we could not confirm previous studies suggesting MBL deficiency to be associated with an increased risk for CVD.


Assuntos
Hipertensão , Lectina de Ligação a Manose/deficiência , Erros Inatos do Metabolismo , Adulto , Fatores Etários , Feminino , Humanos , Hipertensão/epidemiologia , Hipertensão/etiologia , Hipertensão/genética , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/genética , Masculino , Lectina de Ligação a Manose/genética , Erros Inatos do Metabolismo/epidemiologia , Erros Inatos do Metabolismo/genética , Pessoa de Meia-Idade , Fatores de Risco
7.
Pediatr Pulmonol ; 55(5): 1190-1198, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32119194

RESUMO

BACKGROUND: Mannose-binding lectin (MBL) is a complement protein involved in the innate immune system, and is associated with some chronic respiratory diseases including noncystic fibrosis (non-CF) bronchiectasis in adults. The aim of this study was to investigate the frequency of MBL2 gene polymorphisms in children with non-CF bronchiectasis, and the effect of MBL deficiency on disease severity. METHODS: Fifty children with non-CF bronchiectasis (bronchiectasis group) and 50 healthy controls (control group) were included. The demographic findings, number of acute pulmonary exacerbations in the previous year, airway cultures, pulmonary function tests, and radiologic scores of the bronchiectasis group were recorded. DNA extraction was performed in both groups and MBL2 gene polymorphisms in codons 52, 54, 57 in exon 1 and H/L, Y/X in the promoter region were studied using real-time polymerase chain reaction. Haplotypes were made by genotypes, and MBL serum expression was classified according to the genotypes in the literature. RESULTS: The bronchiectasis group consisted of 23 (46%) patients with primary ciliary dyskinesia, 5 (10%) with primary immunodeficiency diseases, and 22 (44%) with idiopathic bronchiectasis. There were no statistically significant differences between the bronchiectasis and control groups in terms of allele and genotype frequencies of polymorphisms in codons 52, 54, 57 in exon 1 and promoter H/L. However, the YX heterozygote genotype was more frequent in the control group (82%) compared with the bronchiectasis group (50%) (P = .002). The frequency of patients with intermediate serum MBL expression genotype was higher in the bronchiectasis group (20%) than in the control group (0%) (P = .001). In the bronchiectasis group, there were no significant differences in growth, annual pulmonary exacerbation rates in the last year, pulmonary function tests, radiologic scores, and microbiologic findings between low, intermediate, and high-expressing genotypes. CONCLUSIONS: In children with non-CF bronchiectasis, MBL genotype was different from healthy controls. MBL deficiency associated only with MBL genotype was not related to disease severity in this group of patients.


Assuntos
Bronquiectasia/genética , Lectina de Ligação a Manose/genética , Adolescente , Bronquiectasia/fisiopatologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Genótipo , Humanos , Lactente , Pulmão/fisiopatologia , Masculino , Lectina de Ligação a Manose/deficiência , Erros Inatos do Metabolismo/genética , Erros Inatos do Metabolismo/fisiopatologia , Polimorfismo Genético , Testes de Função Respiratória , Índice de Gravidade de Doença
8.
Malar J ; 19(1): 25, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941497

RESUMO

BACKGROUND: Blackwater fever (BWF), one of the most severe and life-threatening forms of falciparum malaria, is characterized by acute massive intravascular haemolysis, often leading to acute renal failure. Thus far, the genetics of the underlying susceptibility to develop BWF is not fully elucidated. Deficiency in the MBL protein, an important component of the innate immune system, has previously been suggested to be a susceptibility factor for the development of severe malaria. This study aimed to evaluate the association between MBL2 gene polymorphisms, known to affect the MBL protein level/activity, and the occurrence of BWF among Congolese children. METHODS: This is a case-control study. Cases were patients with BWF, whereas controls, matched for gender and age, had uncomplicated malaria (UM). Dried blood spot was collected for genotyping. RESULTS: A total of 129 children were screened, including 43 BWF and 86 UM. The common allele in BWF and UM was A, with a frequency of 76.7 and 61.0%, respectively (OR: 2.67 (0.87-829) and p = 0.079). The frequency of the C allele was 18.6 and 29.1% in BWF and UM groups, respectively, with p = 0.858. Not a single D allele was encountered. Genotype AA was at higher risk for BWF whereas genotypes A0 (AB and AC) were over-represented in UM group (OR: 0.21 (0.06-0.78)) with p = 0.019. Nine haplotypes were observed in this study: 3 high MBL expression haplotypes and 6 low MBL expression haplotype. One new haplotype HYPC was observed in this study. None of these haplotypes was significantly associated with BWF. CONCLUSION: This pilot study is a preliminary research on MBL2 gene and infectious diseases in DRC. The study results show a higher risk for BWF in AA. This suggests that future studies on BWF should further investigate the contribution of a strong immune response to the occurrence of BWF.


Assuntos
Febre Hemoglobinúrica/epidemiologia , Febre Hemoglobinúrica/genética , Lectina de Ligação a Manose/genética , Polimorfismo Genético , Adolescente , Alelos , Febre Hemoglobinúrica/urina , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , DNA/genética , DNA/isolamento & purificação , República Democrática do Congo/epidemiologia , Feminino , Frequência do Gene , Técnicas de Genotipagem , Haplótipos , Hemoglobinúria/diagnóstico , Hemoglobinúria/urina , Humanos , Modelos Logísticos , Masculino
10.
J Matern Fetal Neonatal Med ; 33(1): 127-135, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29886784

RESUMO

Background: The mannose-binding lectin (MBL2) and nitric oxide synthase 3 (NOS3) genes are associated with the immune response against inflammatory processes, have been reported as possibly related with premature birth. Until now, most of the researches regarding the genetic influence of prematurity have revealed limited results because only investigating the child or the mothers' genotypes, thus not exploring the possible effects of interactions between these genotypes or the interactions with environmental factors related to the duration of pregnancy.Objective: We performed a replica study investigating the influence of single nucleotide polymorphisms (SNPs) in MBL2 and NOS3 genes on premature birth, also considering socioeconomic, demographic, and gestational factors.Materials and methods: We conducted a case-control study with 189 mother-infant dyads, with 104 spontaneous preterm births and 85 term births from Recife, Brazil. We used peripheral blood samples and umbilical cord samples to extract DNA. Functional SNPs at exon 1 and promoter region of MBL2 and NOS3 RS1799983 SNP were genotyped using direct sequencing and fluorescent allelic specific TaqMan® assays respectively. Data were analyzed using the Statistical Package for the Social Sciences (SPSS®) program with bivariate association and logistic multivariate regression tests.Results: We observed a prevalence of MBL2 wild-type genotype in the mother-infant dyad of the preterm group and polymorphic genotype in the mother-infant dyad of term birth. The haplotype LYA predominated in our sample, being more frequent in the preterm group, while the haplotype LYB, correlated with lower levels of MBL protein, was more frequent in the term birth group. About NOS3 RS1799983 SNP, the G/G genotype was more frequent throughout the sample. The heterozygous genotype predominated among women from the preterm group, showed a borderline difference between the groups. When MBL2 genotypes of the mother and son were analyzed together, codon 54 of MBL2 remained associated with prematurity. When the variables with p value lower than .20 in the bivariate analysis were analyzed by logistic regression, the low weight of the pregnant woman in relation to the gestational age, the occurrence of preterm premature rupture of membranes, urinary tract infection during birth and maternal history of other premature births were risk factors to prematurity. On the other hand, the presence of B allele at codon 54 of maternal MBL2 was a protective factor for the occurrence of spontaneous premature birth. In contrast, a borderline association was established between the maternal genetic variation within NOS3 gene and the outcome studied.Conclusions: Our study, limited by the small number of patients enrolled, indicates that MBL2 and NOS3 functional SNPs are associated with the occurrence of spontaneous prematurity and the regulation of the maternal inflammatory response. Despite these results are in agreement with previously reports, our findings do not replicate the ones reported in a large genome-wide association study performed on quite high number of subjects. Thus, we can conclude that MBL2 and NOS3 functional SNPs are plausible candidate risk factors just in few preterm birth cases, and consequently they cannot be included in the general diagnostic practice.


Assuntos
Lectina de Ligação a Manose/genética , Óxido Nítrico Sintase Tipo III/genética , Polimorfismo de Nucleotídeo Único , Nascimento Prematuro/genética , Adolescente , Adulto , Brasil/epidemiologia , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Recém-Nascido , Gravidez , Nascimento Prematuro/epidemiologia , Adulto Jovem
11.
J Clin Pathol ; 73(6): 318-321, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31767616

RESUMO

AIMS: Associations between polymorphisms in cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)/mannose-binding lectin (MBL)/interleukin-4 (IL-4)/interleukin-6 (IL-6)/phospholipase C ε-1 (PLCE1) and gastric cancer (GC) were already reported by many studies, yet the conclusions of these studies were somehow controversial. The aim of this meta-analysis was to better clarify associations between polymorphisms in CTLA-4/MBL/IL-4/IL-6/PLCE1 and GC by combing the results of all relevant studies. METHODS: Eligible studies were searched from PubMed, Embase, WOS and CNKI. We used Review Manager to combine the results of individual studies. RESULTS: Forty-three studies were included in this meta-analysis. Combined results revealed that CTLA-4 rs5742909 (dominant comparison: OR: 1.58, 95 % CI: 1.01 to 2.48; allele comparison: OR: 1.69, 95 % CI: 1.12 to 2.56) and PLCE1 rs2274223 (dominant comparison: OR: 0.84, 95 % CI: 0.72 to 0.98; recessive comparison: OR: 1.23, 95 % CI: 1.08 to 1.40; over-dominant comparison: OR: 1.16, 95 % CI: 1.00 to 1.34; allele comparison: OR 0.88, 95 % CI 0.78 to 0.99) polymorphisms were significantly associated with GC in the general population. We also obtained similar significant associations with GC for rs5742909 and rs2274223 polymorphisms in East Asians. Nevertheless, no positive results were observed for the other eight investigated polymorphisms. CONCLUSION: Collectively, this meta-analysis demonstrated that CTLA-4 rs5742909 and PLCE1 rs2274223 polymorphisms may confer susceptibility to GC, especially for East Asians.


Assuntos
Antígeno CTLA-4/genética , Lectina de Ligação a Manose/genética , Fosfoinositídeo Fosfolipase C/genética , Polimorfismo Genético/genética , Neoplasias Gástricas/genética , Predisposição Genética para Doença , Humanos , Interleucina-4/genética , Interleucina-6/genética
12.
World J Surg Oncol ; 17(1): 216, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31830994

RESUMO

BACKGROUND: Associations between polymorphisms in vitamin D receptor (VDR)/vascular endothelial growth factor (VEGF)/interleukin-18 (IL-18)/mannose-binding lectin (MBL) and susceptibility to hepatocellular carcinoma (HCC) were already explored by many studies, yet the results of these studies were inconsistent. The aim of this meta-analysis was to better clarify associations between polymorphisms in VDR/VEGF/IL-18/MBL and HCC by combing the results of all relevant studies. METHODS: Eligible publications were searched from PubMed, Embase, WOS, and CNKI. We used Review Manager to combine the results of individual studies. RESULTS: Thirty studies were included in this study. Combined results revealed that VDR rs7975232, VDR rs2228570, VEGF rs699947, VEGF rs3025039, IL-18 rs1946518, and MBL rs7096206 polymorphisms were all significantly associated with HCC in the overall pooled population. We also obtained similar significant associations for VDR rs7975232, VDR rs2228570, IL-18 rs1946518, and MBL rs7096206 polymorphisms in Asians. CONCLUSIONS: Collectively, this meta-analysis proved that VDR rs7975232, VDR rs2228570, VEGF rs699947, VEGF rs3025039, IL-18 rs1946518, and MBL rs7096206 polymorphisms may confer susceptibility to HCC in certain populations.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Carcinoma Hepatocelular/patologia , Predisposição Genética para Doença , Humanos , Interleucina-18/genética , Neoplasias Hepáticas/patologia , Lectina de Ligação a Manose/genética , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol/genética , Fator A de Crescimento do Endotélio Vascular/genética
13.
BMC Plant Biol ; 19(1): 561, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31852472

RESUMO

BACKGROUND: Jacalin-related lectins in plants are important in defense signaling and regulate growth, development, and response to abiotic stress. We characterized the function of a rice mannose-binding jacalin-related lectin (OsJAC1) in the response to DNA damage from gamma radiation. RESULTS: Time- and dose-dependent changes of OsJAC1 expression in rice were detected in response to gamma radiation. To identify OsJAC1 function, OsJAC1-overexpressing transgenic Arabidopsis plants were generated. Interestingly, OsJAC1 overexpression conferred hyper-resistance to gamma radiation in these plants. Using comparative transcriptome analysis, genes related to pathogen defense were identified among 22 differentially expressed genes in OsJAC1-overexpressing Arabidopsis lines following gamma irradiation. Furthermore, expression profiles of genes associated with the plant response to DNA damage were determined in these transgenic lines, revealing expression changes of important DNA damage checkpoint and perception regulatory components, namely MCMs, RPA, ATM, and MRE11. CONCLUSIONS: OsJAC1 overexpression may confer hyper-resistance to gamma radiation via activation of DNA damage perception and DNA damage checkpoints in Arabidopsis, implicating OsJAC1 as a key player in DNA damage response in plants. This study is the first report of a role for mannose-binding jacalin-related lectin in DNA damage.


Assuntos
Arabidopsis/efeitos da radiação , Regulação da Expressão Gênica de Plantas/genética , Lectina de Ligação a Manose/genética , Oryza/genética , Proteínas de Plantas/genética , Radiação Ionizante , Protetores contra Radiação/metabolismo , Lectina de Ligação a Manose/metabolismo , Oryza/metabolismo , Lectinas de Plantas/metabolismo , Proteínas de Plantas/metabolismo
14.
BMC Immunol ; 20(1): 40, 2019 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-31706269

RESUMO

BACKGROUND: Mannose-binding lectin (MBL) is a key component of innate immunity. Low serum MBL levels, related to promoter polymorphism and structural variants, have been associated with an increased risk of infection. The aim of this work was to analyse the incidence and severity of infections and mortality in relation to the MBL2 genotype and MBL levels in patients underwent allogeneic haematopoietic stem cell transplantation (Allo-HSCT). RESULTS: This was a prospective cohort study of 72 consecutive patients underwent Allo-HSCT between January 2007 and June 2009 in a tertiary referral centre. Three periods were considered in the patients' follow-up: the early period (0-30 days after Allo-HSCT), the intermediate period (30-100 days after Allo-HSCT) and the late period (> 100 days after Allo-HSCT). A commercial line probe assay for MBL2 genotyping and an ELISA Kit were used to measure MBL levels. A total of 220 episodes of infection were collected in the 72 patients. No association between donor or recipient MBL2 genotype and infection was found. The first episode of infection presented earlier in patients with pre-transplant MBL levels of < 1000 ng/ml (median 6d vs 8d, p = 0.036). MBL levels < 1000 ng/ml in the pre-transplant period (risk ratio (RR) 2.48, 95% CI 1.00-6.13), neutropenic period (0-30 days, RR 3.28, 95% CI 1.53-7.06) and intermediate period (30-100 days, RR 2.37, 95% CI 1.15-4.90) were associated with increased risk of virus infection. No association with bacterial or fungal disease was found. Mortality was associated with pre-transplant MBL levels < 1000 ng/ml (hazard ratio 5.55, 95% CI 1.17-26.30, p = 0.03) but not with MBL2 genotype. CONCLUSIONS: Patients who underwent Allo-HSCT with low pre-transplant MBL levels presented the first episode of infection earlier and had an increased risk of viral infections and mortality in the first 6 months post-transplant. Thus, pre-transplant MBL levels would be important in predicting susceptibility to viral infections and mortality and might be considered a biomarker to be included in the pre-transplantation risk assessment.


Assuntos
Suscetibilidade a Doenças , Expressão Gênica , Transplante de Células-Tronco Hematopoéticas , Lectina de Ligação a Manose/genética , Viroses/etiologia , Viroses/mortalidade , Adolescente , Adulto , Biomarcadores , Feminino , Predisposição Genética para Doença , Genótipo , Doenças Hematológicas/complicações , Doenças Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Lectina de Ligação a Manose/sangue , Pessoa de Meia-Idade , Polimorfismo Genético , Período Pré-Operatório , Prognóstico , Transplante Homólogo , Viroses/diagnóstico , Adulto Jovem
15.
PLoS Genet ; 15(9): e1008393, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31525185

RESUMO

Type IV pili are dynamic cell surface appendages found throughout the bacteria. The ability of these structures to undergo repetitive cycles of extension and retraction underpins their crucial roles in adhesion, motility and natural competence for transformation. In the best-studied systems a dedicated retraction ATPase PilT powers pilus retraction. Curiously, a second presumed retraction ATPase PilU is often encoded immediately downstream of pilT. However, despite the presence of two potential retraction ATPases, pilT deletions lead to a total loss of pilus function, raising the question of why PilU fails to take over. Here, using the DNA-uptake pilus and mannose-sensitive haemagglutinin (MSHA) pilus of Vibrio cholerae as model systems, we show that inactivated PilT variants, defective for either ATP-binding or hydrolysis, have unexpected intermediate phenotypes that are PilU-dependent. In addition to demonstrating that PilU can function as a bona fide retraction ATPase, we go on to make the surprising discovery that PilU functions exclusively in a PilT-dependent manner and identify a naturally occurring pandemic V. cholerae PilT variant that renders PilU essential for pilus function. Finally, we show that Pseudomonas aeruginosa PilU also functions as a PilT-dependent retraction ATPase, providing evidence that the functional coupling between PilT and PilU could be a widespread mechanism for optimal pilus retraction.


Assuntos
Adenosina Trifosfatases/genética , Proteínas de Fímbrias/metabolismo , Fímbrias Bacterianas/metabolismo , Adenosina Trifosfatases/metabolismo , Proteínas de Bactérias/genética , Proteínas de Fímbrias/genética , Proteínas de Fímbrias/fisiologia , Fímbrias Bacterianas/fisiologia , Lectina de Ligação a Manose/genética , Lectina de Ligação a Manose/metabolismo , Proteínas Motores Moleculares/genética , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo , Vibrio cholerae/genética , Vibrio cholerae/metabolismo
16.
BMC Med Genomics ; 12(1): 130, 2019 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-31519222

RESUMO

BACKGROUND: Pneumonia, sepsis, meningitis, and empyema due to Streptococcus pneumoniae is a major cause of morbidity and mortality. We provide a systemic overview of genetic variants associated with susceptibility, phenotype and outcome of community acquired pneumococcal pneumonia (CAP) and invasive pneumococcal disease (IPD). METHODS: We searched PubMed for studies on the influence of host genetics on susceptibility, phenotype, and outcome of CAP and IPD between Jan 1, 1983 and Jul 4, 2018. We listed methodological characteristics and when genetic data was available we calculated effect sizes. We used fixed or random effect models to calculate pooled effect sizes in the meta-analysis. RESULTS: We identified 1219 studies of which 60 studies involving 15,358 patients were included. Twenty-five studies (42%) focused on susceptibility, 8 (13%) on outcome, 1 (2%) on disease phenotype, and 26 (43%) on multiple categories. We identified five studies with a hypothesis free approach of which one resulted in one genome wide significant association in a gene coding for lincRNA with pneumococcal disease susceptibility. We performed 17 meta-analyses of which two susceptibility polymorphisms had a significant overall effect size: variant alleles of MBL2 (odds ratio [OR] 1·67, 95% confidence interval [CI] 1·04-2·69) and a variant in CD14 (OR 1·77, 95% CI 1·18-2·66) and none of the outcome polymorphisms. CONCLUSIONS: Studies have identified several host genetics factors influencing risk of pneumococcal disease, but many result in non-reproducible findings due to methodological limitations. Uniform case definitions and pooling of data is necessary to obtain more robust findings.


Assuntos
Infecções Pneumocócicas/genética , Polimorfismo Genético , Suscetibilidade a Doenças , Humanos , Receptores de Lipopolissacarídeos/genética , Lectina de Ligação a Manose/genética , Razão de Chances , Fenótipo , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/patologia , RNA Longo não Codificante/metabolismo , Fatores de Risco
17.
Am J Trop Med Hyg ; 101(6): 1322-1324, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31549610

RESUMO

Mannose-binding lectin (MBL) and MBL-associated serine protease-2 (MASP-2) are important proteins in the lectin pathway of the immune system. Mannose-binding lectin and MASP-2 deficiencies have been reported to be responsible for various fungal infections. We investigated the association of MBL and MASP-2 variants with sporotrichosis in a Chinese population and revealed one rare heterozygous mutation in a disseminated cutaneous patient without immunosuppressive conditions (MASP2, p.156_159dupCHNH). We also found that sporotrichosis patients had decreased levels of MBL and MASP-2 in their serum samples compared with controls. Our findings linked, for the first time, MASP-2 deficiencies with susceptibility to Sporothrix sp.


Assuntos
Genótipo , Lectina de Ligação a Manose/sangue , Lectina de Ligação a Manose/genética , Serina Proteases Associadas a Proteína de Ligação a Manose/genética , Esporotricose/genética , Grupo com Ancestrais do Continente Asiático , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Heterozigoto , Humanos , Masculino , Serina Proteases Associadas a Proteína de Ligação a Manose/deficiência , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
18.
Pathog Dis ; 77(7)2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31381758

RESUMO

Some previous genetic association studies have tried to investigate potential associations between mannose-binding lectin (MBL) polymorphisms and viral hepatitis. However, the results of those studies were not consistent. Therefore, we performed the current meta-analysis to explore associations between MBL polymorphisms and viral hepatitis in a large pooled population. A systematic literature research of PubMed, Web of Science, Embase and CNKI was performed to identify eligible studies for pooled analyses. We used Review Manager version 5.3.3 to conduct statistical analyses. In total, 27 studies were included for analysis (4840 cases and 5729 controls). The pooled analyses showed that MBL promoter (-211C/G, dominant model: P = 0.0002, I2 = 40%; over-dominant model: P = 0.0001, I2 = 22%) and exon 1 (codon 52, 54 and 57, dominant model: P = 0.04, I2 = 49%; allele model: P = 0.01, I2 = 48%) polymorphisms were both significantly associated with viral hepatitis in the overall population. Further subgroup analyses revealed similarly significant findings for MBL promoter polymorphism in HBV and HCV, but no positive results were detected in subgroup analyses for MBL exon 1 polymorphism. These results suggested that MBL promoter and exon 1 polymorphisms could be used to identify individuals at higher susceptibility to HBV and HCV.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Hepatite Viral Humana/diagnóstico , Hepatite Viral Humana/genética , Lectina de Ligação a Manose/genética , Polimorfismo de Nucleotídeo Único , Alelos , Estudos de Associação Genética/métodos , Genótipo , Humanos , Razão de Chances , Viés de Publicação
19.
Infect Genet Evol ; 75: 104015, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31446139

RESUMO

BACKGROUND: The role of (MBL) gene single nucleotide polymorphisms (SNPs) has been well documented in susceptibility to several infectious diseases. This study aimed to investigate the association between two MBL promoter variants, -550 H/L and -221 X/Y, and susceptibility to HTLV-1 infection. METHODS: A total of 153 subjects infected with HTLV-1 and 169 healthy controls were recruited. SSP-PCR method was applied to genotype -550 H/L and -221 X/Y polymorphisms. Associations between genotypes or alleles and susceptibility to HTLV-1 infection were analyzed by Pearson's Chi-Square. p ≤ .05 was considered statistically significant. RESULTS: Statistical analysis revealed significant differences between the two groups in the -221 position (χ2 = 19.709; p = .000). The MBL YX genotype was significantly associated with increased susceptibility to HTLV-1 (OR = 2.73, %95 CI = 1.74-4.30). Combined genotype of the two loci showed that the HYHX genotype (OR = 2.20, 95% CI = 1.95-2.48) and LYLX (OR = 1.97, 95% CI = 1.13-3.45) were associated with an increased risk of HTLV-1 infection. CONCLUSION: Our results represent the importance of -221 X > Y variants in acquisition of HTLV-1 as this is the case for several other viral and bacterial infections.


Assuntos
Predisposição Genética para Doença , Infecções por HTLV-I/etiologia , Vírus Linfotrópico T Tipo 1 Humano , Lectina de Ligação a Manose/genética , Polimorfismo de Nucleotídeo Único , Alelos , Substituição de Aminoácidos , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Genótipo , Infecções por HTLV-I/diagnóstico , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Razão de Chances , Regiões Promotoras Genéticas
20.
Egypt J Immunol ; 26(1): 91-99, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31332999

RESUMO

Immature immune system in neonates is considered a risk factor for neonatal infections and sepsis. Mannose-binding lectin (MBL) is one of the innate immune system components that could recognize a wide variety of pathogens and initiate an immune response against them. Objectives of this study were to assess the correlation between serum level of MBL and MBL2 gene polymorphism and incidence of neonatal sepsis. Isolation of bacteria from neonatal blood culture was carried out by conventional methods then, serum level of MBL was measured by ELISA and MBL2 gene polymorphism was determined by PCR-RFLP. Out of 50 neonates with sepsis enrolled in this study, 44 (88%) neonates had MBL deficiency and 6 (12%) had normal serum level with a very high statistically significant difference (P=0.00001). Genotype BB was more frequent in neonatal sepsis (56%) followed by genotype AB (32%) then genotype AA (12%) and it was more prevalent in preterm (63.2%) than in full term (33.3%) with a high statistically significant difference (P=0.001). Patients with BB genotype had the lowest MBL level in serum compared to other genotypes with a very high significant difference (P=0.001). In conclusion, low serum level of MBL and genotype BB might be significantly associated with development of sepsis among neonates.


Assuntos
Lectina de Ligação a Manose/sangue , Lectina de Ligação a Manose/genética , Sepse Neonatal/sangue , Polimorfismo Genético , Genótipo , Hospitais Universitários , Humanos , Recém-Nascido , Recém-Nascido Prematuro
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