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

Abstract\ud \ud Background\ud 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.\ud \ud \ud Methods\ud 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.\ud \ud \ud Results\ud 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).\ud \ud \ud Conclusions\ud 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

A Polymorphism in the TMPRSS2 Gene Increases the Risk of Death in Older Patients Hospitalized with COVID-19

Background: Transmembrane serine protease type 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2) are the main molecules involved in the entry of SARS-CoV-2 into host cells. Changes in TMPRSS2 expression levels caused by single nucleotide polymorphisms (SNPs) may contribute to the outcome of COVID-19. The aim was to investigate the association between TMPRSS2 gene polymorphisms and the risk of death in hospitalized patients with COVID-19. Methods: We included patients with confirmed COVID-19, recruited from two hospitals in northeastern Brazil from August 2020 to July 2021. Two functional polymorphisms (rs2070788 and rs12329760) in TMPRSS2 were evaluated by real-time PCR. The Kaplan–Meier method was used to estimate death. The Cox’s proportional hazards model was used to adjust for potentially confounding factors. Results: A total of 402 patients were followed prospectively. Survival analysis demonstrated that older patients carrying the rs2070788 GG genotype had shorter survival times when compared to those with AG or AA genotypes (p = 0.009). In multivariable analysis, the GG genotype was a factor independently associated with the risk of death in older individuals (hazard ratio = 4.03, 95% confidence interval 1.49 to 10.84). Conclusions: The rs2070788 polymorphism in TMPRSS2 increases risk of death four-fold in older patients hospitalized with COVID-19

Mannose-binding lectin 2 (MBL2) gene polymorphisms do not influence frequency of infections in chronic lymphocytic leukemia patients

Background: Infectious complications represent the main cause of morbidity and mortality in chronic lymphocytic leukemia. It has been reported that polymorphisms of the mannosebinding lectin 2 (MBL2) genes are correlated with MBL protein serum levels and, consequently, are associated with the development of infectious diseases. Objective: The purpose of this study was to investigate the possible association between MBL2 gene polymorphisms and risk of infection in chronic lymphocytic leukemia patients. Methods: Peripheral blood samples from 116 chronic lymphocytic leukemia patients were collected; after genomic DNA extraction, real time polymerase chain reaction was used to determine the polymorphisms of the promoter region and exon 1 of the MBL2 gene. Results: A high frequency of Binet stage A (p-value = 0.005) and absence of splenomegaly (p-value = 0.002) were observed in patients with no infection; however, variant alleles/ genotypes and haplotypes of this gene had no impact on the risk of infection. Conclusion: To the authors' knowledge, this is the first study describing the association between MBL2 polymorphisms and infectious disease in chronic lymphocytic leukemia. Although it was not possible to demonstrate any influence of MBL2 polymorphisms as a genetic modulator of infection in chronic lymphocytic leukemia, the authors believe that the present data are clinically relevant and provide the basis for future studies

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

Submitted by Ana Beatriz Oliveira ([email protected]) on 2018-12-28T12:52:31Z No. of bitstreams: 1 1-s2.0-S120197121100097X-main.pdf: 475674 bytes, checksum: 9c9f87b59212693bedca0418d9a58b77 (MD5)Approved for entry into archive by Ana Beatriz Oliveira ([email protected]) on 2018-12-28T13:12:26Z (GMT) No. of bitstreams: 1 1-s2.0-S120197121100097X-main.pdf: 475674 bytes, checksum: 9c9f87b59212693bedca0418d9a58b77 (MD5)Made available in DSpace on 2018-12-28T13:12:26Z (GMT). No. of bitstreams: 1 1-s2.0-S120197121100097X-main.pdf: 475674 bytes, checksum: 9c9f87b59212693bedca0418d9a58b77 (MD5) Previous issue date: 2011FACEPE (Fundação de Amparo à Ciência e Tecnologia do Estado de Pernambuco) and Programa de Pós-Graduação em Bolsas da Universidade de Pernambuco.Universidade de Pernambuco. Instituto de Ciências Biológicas. Faculdade de Ciências Medicas. Recife PE, Brasil. / Instituto do Fígado de Pernambuco. Recife PE, Brasil.Universidade de Pernambuco. Instituto de Ciências Biológicas. Faculdade de Ciências Medicas. Recife PE, Brasil.Universidade de Pernambuco. Instituto de Ciências Biológicas. Faculdade de Ciências Medicas. Recife PE, Brasil.Universidade de Pernambuco. Instituto de Ciências Biológicas. Faculdade de Ciências Medicas. Recife PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil. / Instituto de Medicina Integral Professor Fernando Figueira. Recife PE, Brasil.Universidade de Pernambuco. Instituto de Ciências Biológicas. Faculdade de Ciências Medicas. Recife PE, Brasil. / Instituto do Fígado de Pernambuco. Recife PE, Brasil.Universidade de Pernambuco. Instituto de Ciências Biológicas. Faculdade de Ciências Medicas. Recife PE, Brasil.Universidade de Pernambuco. Instituto de Ciências Biológicas. Faculdade de Ciências Medicas. Recife PE, Brasil.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

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

Submitted by Adagilson Silva ([email protected]) on 2017-06-05T13:08:05Z No. of bitstreams: 1 27603703 2016 men-sin.oa.PDF: 1008770 bytes, checksum: 82f0081628ade062bc08ce6be5782a03 (MD5)Approved for entry into archive by Adagilson Silva ([email protected]) on 2017-06-05T13:08:29Z (GMT) No. of bitstreams: 1 27603703 2016 men-sin.oa.PDF: 1008770 bytes, checksum: 82f0081628ade062bc08ce6be5782a03 (MD5)Made available in DSpace on 2017-06-05T13:08:29Z (GMT). No. of bitstreams: 1 27603703 2016 men-sin.oa.PDF: 1008770 bytes, checksum: 82f0081628ade062bc08ce6be5782a03 (MD5) Previous issue date: 2016Programa de Doutorado da Rede Nordeste de Biotecnologia. Recife, PE, Brasil.Universidade de Pernambuco. Instituto de Ciências Biológicas e Faculdade de Ciências Médicas. Recife, PE, Brasil.Universidade de Pernambuco. Instituto de Ciências Biológicas e Faculdade de Ciências Médicas. Recife, PE, Brasil.Universidade Federal de Pernambuco. Laboratório de Imunomodulação e Novas Abordagens Terapêutica (LINAT). Recife, PE, Brasil.Universidade de Pernambuco. Instituto de Ciências Biológicas e Faculdade de Ciências Médicas. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.Fundação Hematologia e Hemoterapia de Pernambuco (HEMOPE). Recife, PE, Brasil.Universidade Federal de Pernambuco. Departamento de Ciências Biológicas. Recife, PE, Brasil.Universidade Federal de Pernambuco. Laboratório de Imunomodulação e Novas Abordagens Terapêutica (LINAT). Recife, PE, Brasil.Universidade Federal de Pernambuco. Departamento de Ciências Biológicas. Recife, PE, Brasil.Fundação Hematologia e Hemoterapia de Pernambuco (HEMOPE). Recife, PE, Brasil.Universidade Federal de Pernambuco. Laboratório de Imunomodulação e Novas Abordagens Terapêutica (LINAT). Recife, PE, Brasil.Programa de Doutorado da Rede Nordeste de Biotecnologia. Recife, PE, Brasil / Universidade de Pernambuco. Instituto de Ciências Biológicas e Faculdade de Ciências Médicas. Recife, PE, Brasil.Programa de Doutorado da Rede Nordeste de Biotecnologia. Recife, PE, Brasil / Universidade de Pernambuco. Instituto de Ciências Biológicas e Faculdade de Ciências Médicas. Recife, PE, Brasil.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

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

Abstract 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

Association of the SOD2 Polymorphism (Val16Ala) and SOD Activity with Vaso-occlusive Crisis and Acute Splenic Sequestration in Children with Sickle Cell Anemia

Submitted by Paulo Silva ([email protected]) on 2019-11-18T13:17:51Z No. of bitstreams: 1 Association of the SOD2 Polymorphism (Val16Ala) and SOD Activity with Vaso-occlusive Crisis and Acute Splenic Sequestration in Children with Sickle Cell Anemia.pdf: 335007 bytes, checksum: a614766bb4931821c7294ae8bbbed5e6 (MD5)Approved for entry into archive by Paulo Silva ([email protected]) on 2019-11-18T13:55:11Z (GMT) No. of bitstreams: 1 Association of the SOD2 Polymorphism (Val16Ala) and SOD Activity with Vaso-occlusive Crisis and Acute Splenic Sequestration in Children with Sickle Cell Anemia.pdf: 335007 bytes, checksum: a614766bb4931821c7294ae8bbbed5e6 (MD5)Made available in DSpace on 2019-11-18T13:55:11Z (GMT). No. of bitstreams: 1 Association of the SOD2 Polymorphism (Val16Ala) and SOD Activity with Vaso-occlusive Crisis and Acute Splenic Sequestration in Children with Sickle Cell Anemia.pdf: 335007 bytes, checksum: a614766bb4931821c7294ae8bbbed5e6 (MD5) Previous issue date: 2018FACEPEUniversidade de Pernambuco. Instituto de Ciências Biológicas. Recife, PE, Brasil.Universidade de Pernambuco. Instituto de Ciências Biológicas. Recife, PE, Brasil / Universidade Federal Rural de Pernambuco. Programa de Pós-Graduação em Biotecnologia. Recife, PE, Brasil.Universidade de Pernambuco. Instituto de Ciências Biológicas. Recife, PE, Brasil.Universidade de Pernambuco. Instituto de Ciências Biológicas. Recife, PE, Brasil.Universidade Federal de Pernambuco. Recife, PE, Brasil.Universidade de Pernambuco. Instituto de Ciências Biológicas. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.Universidade Federal de Pernambuco. Recife, PE, Brasil / Fundação de Hematologia e Hemoterapia de Pernambuco. Recife, PE, Brasil.Fundação de Hematologia e Hemoterapia de Pernambuco. Recife, PE, Brasil.Universidade de Pernambuco. Instituto de Ciências Biológicas. Recife, PE, Brasil.Universidade Federal de Pernambuco. Recife, PE, Brasil.Fundação de Hematologia e Hemoterapia de Pernambuco. Recife, PE, Brasil.Universidade de Pernambuco. Instituto de Ciências Biológicas. Recife, PE, Brasil / Fundação de Hematologia e Hemoterapia de Pernambuco. Recife, PE, Brasil.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