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

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

Serum galectin-3 levels associated with <i>LGALS3</i> +191 (A) and +292 (B) genotypes in children with SCA.

<p><i>LGALS3</i> +191: C = reference allele; A = variant allele; <i>LGALS3</i> +292: A = reference allele; C = variant allele; +191 genotypes: CC vs. CA: <i>p <</i>0.0001; CC vs. AA: <i>p <</i>0.0001; CC vs. AA+CA: <i>p</i> <0.0001. +292 genotypes: AA vs. AC: <i>p</i> = 0.1684; AA vs. CC: <i>p</i> = 0.0046; AA vs. CC+AC: <i>p</i> = 0.0136. Mann-Whitney tests.</p

Clinical data of children with sickle cell anemia attended in Hemope Foundation—Recife/Brazil.

<p>Clinical data of children with sickle cell anemia attended in Hemope Foundation—Recife/Brazil.</p

Serum galectin-3 levels are associated with <i>LGALS3</i> +191 and +292 combined genotypes in children with SCA.

<p>Statistical analysis of <i>LGALS3</i> combined genotype related of galectin-3 levels (high, intermediate and low) in which the serum concentrations in ng/ml were compared using Kruskal-Wallis test. High vs. intermediate: <i>p =</i> 0.1687; high vs. low: <i>p =</i> 0.0002; high vs. intermediate+low: <i>p</i> = 0.0098.</p

<i>LGALS3</i> +191 and +292 diplotype of serum levels with vaso-occlusive crisis and respiratory tract infection in children with sickle cell anemia attended in Hemope Foundation—Recife/Brazil.

<p><i>LGALS3</i> +191 and +292 diplotype of serum levels with vaso-occlusive crisis and respiratory tract infection in children with sickle cell anemia attended in Hemope Foundation—Recife/Brazil.</p

<i>LGALS3</i> +191 and +292 combined genotype distribution with vaso-occlusive crisis and respiratory tract infection in children with sickle cell anemia attended in Hemope Foundation—Recife/Brazil.

<p><i>LGALS3</i> +191 and +292 combined genotype distribution with vaso-occlusive crisis and respiratory tract infection in children with sickle cell anemia attended in Hemope Foundation—Recife/Brazil.</p

<i>LGALS3</i> +191 and +292 with vaso-occlusive crisis and respiratory tract infection in children with sickle cell anemia attended in Hemope Foundation—Recife/Brazil.

<p><i>LGALS3</i> +191 and +292 with vaso-occlusive crisis and respiratory tract infection in children with sickle cell anemia attended in Hemope Foundation—Recife/Brazil.</p

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

<div><p>Introduction</p><p>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.</p><p>Objective</p><p>To investigate associations between the SNPs of GAL-3 gene (<i>LGALS3</i>) and serum levels with RTI and vaso-occlusive crisis (VOC) in children with SCA.</p><p>Materials and Methods</p><p>SNPs +191 and +292 in <i>LGALS3</i> 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.</p><p>Results</p><p>GAL-3 serum levels were associated with <i>LGALS3</i> +191 and +292 genotypes (<i>p</i> <0.0001; <i>p</i> = 0.0169, respectively). <i>LGALS3</i> +191, AA genotype was associated with low and CC with higher levels of GAL-3. For <i>LGALS3</i> +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 (<i>p</i> = 0.0263) and +292AC/CC genotypes (<i>p</i> = 0.0320). SNP +292 was associated with Frequency of VOC (FVOC) (<i>p</i> = 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 (<i>p</i> = 0.0170; <i>p</i> = 0.0138, respectively). Also, patients with FVOC ≥1 presented association with CA/AC (<i>p</i> = 0.0228). <i>LGALS3</i> +191 and +292 combined genotypes related to low (<i>p</i> = 0.0263) and intermediate expression (<i>p</i> = 0.0245) were associated with FRTI ≥1. Lower GAL-3 serum levels were associated with FRTI ≥1 (<i>p</i> = 0.0426) and FVOC ≥1 (<i>p</i> = 0.0012).</p><p>Conclusion</p><p>Variation of GAL-3 serum levels related to SNPs at +191 and +292 may constitute a susceptibility factor for RTI and VOC frequency.</p></div

Serum galectin-3 levels associated with frequency of respiratory tract infection (FRTI) and vaso-occlusive crisis (FVOC) in children with SCA.

<p>FRTI ≥1 vs. FRTI <1: <i>p</i> = 0.0426. FVOC ≥1 vs. FVOC <1: <i>p</i> = 0.0012. Mann-Whitney tests.</p