Endothelial nitric oxide synthase (-786T>C) and endothelin-1 (5665G>T) gene polymorphisms as vascular dysfunction risk factors in sickle cell anemia

We thank the patients for their participation because without them, this study would not have been conducted.Submitted by Éder Freyre ([email protected]) on 2017-02-13T11:47:48Z No. of bitstreams: 1 ve_Wendell_Vilas-Boas_etal_CPqGM_2016 .pdf: 691946 bytes, checksum: 0913753e32f3eeb2404666e32d916a29 (MD5)Approved for entry into archive by Éder Freyre ([email protected]) on 2017-02-13T12:20:03Z (GMT) No. of bitstreams: 1 ve_Wendell_Vilas-Boas_etal_CPqGM_2016 .pdf: 691946 bytes, checksum: 0913753e32f3eeb2404666e32d916a29 (MD5)Made available in DSpace on 2017-02-13T12:20:03Z (GMT). No. of bitstreams: 1 ve_Wendell_Vilas-Boas_etal_CPqGM_2016 .pdf: 691946 bytes, checksum: 0913753e32f3eeb2404666e32d916a29 (MD5) Previous issue date: 2016Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, Brasil.Fundação de Hematologia e Hemoterapia da Bahia, Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, Brasil / Universidade do Estado da Bahia, Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Hematologia, Genética e Biologia Computacional. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Departamento de Analises Clínicas e Toxicologicas. Salvador, BA, Brasil.Sickle cell anemia (SCA) patients have vascular complications, and polymorphisms in endothelin-1 (ET-1) and endothelial nitric oxide synthase (eNOS) genes were associated with ET-1 and nitric oxide disturbance. We investigate the association of ET-1 5665G>T and eNOS -786T>C polymorphisms with soluble adhesion molecules (sVCAM-1 and sICAM-1), biochemical markers, and medical history. We studied 101 SCA patients; carriers of eNOS minor allele (C) had the highest levels of sVCAM-1, and carriers of ET-1 minor allele had more occurrence of acute chest syndrome (ACS). The multivariate analysis suggested the influence of the ET-1 gene on ACS outcome and an association of the eNOS gene with upper respiratory tract infection. We suggest that eNOS and ET-1 gene polymorphisms can influence SCA pathophysiology and that eNOS variant in SCA patients might be important to nitric oxide activity and vascular alteration. We found an association of the ET-1 minor allele in ACS, showing the importance of genetic screening in SCA

Transforming Growth Factor Beta Receptor 3 Haplotypes in Sickle Cell Disease Are Associated with Lipid Profile and Clinical Manifestations

Individuals with sickle cell disease (SCD) present both chronic and acute inflammatory events. The TGF-β pathway is known to play a role in immune response, angiogenesis, inflammation, hematopoiesis, vascular inflammation, and cell proliferation. Polymorphisms in the transforming growth factor-beta receptor 3 (TGFBR3) gene have been linked to several inflammatory diseases. This study investigated associations between two TGFBR3 haplotypes and classical laboratory parameters, as well as clinical manifestations, in SCD. We found that individuals with the GG haplotype presented higher levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides, non-HDL cholesterol, total proteins, and globulin than individuals with non-GG haplotypes. In addition, the GG haplotype was associated with a previous history of pneumonia. Individuals with the CGG haplotype presented increased plateletcrit, TC, LDL-C levels, and non-HDL cholesterol. The CCG haplotype was also associated with a previous history of pneumonia. Our findings suggest that individuals with the GG and CGG haplotypes of TGFBR3 present important alterations in lipid profile

Hemoglobin Variant Profiles among Brazilian Quilombola Communities

<p>Brazilian Quilombolas are communities composed of African-derived populations that have their territories guaranteed by the Brazilian Constitution. The present study investigated the hemoglobin (Hb) variants among these population groups. This study was conducted in a total of 2843 individuals of Brazilian Quilombola communities of the Bahia, Pará, and Piauí states. All the participants had their Hb profiles evaluated. The Hb S (<i>HBB</i>: c.20A>T) variant was described in all the studied localities. However, the individuals in Bahia State had the highest frequency of the Hb C (<i>HBB</i>: c.19G>A) variant; individuals from Piauí State had a higher frequency of the Hb D-Punjab (<i>HBB</i>: c.364G>C) variant compared to the other states, and individuals from Pará State only carried the Hb S variant. The present study revealed a specific distribution of Hb variants that could represent different waves of African influence in these Brazilian populations.</p

Associations between TGF-β1 Levels and Markers of Hemolysis, Inflammation, and Tissue Remodeling in Pediatric Sickle Cell Patients

Transforming growth factor beta (TGF-β) is a cytokine with important involvement in biological processes related to the pathogenesis of sickle cell disease (SCD), including endothelial and vascular dysfunction, inflammation, and hematopoietic homeostasis. This study is aimed at investigating associations between levels of TGF-β1 and classical laboratory biomarkers and inflammatory mediators, as well as the tissue inhibitor of metalloproteases-1 (TIMP-1) and matrix metalloproteinase-9 (MMP-9), in pediatric patients (n=123) with SCD in steady state: 84 with sickle cell anemia (HbSS) and 39 with hemoglobin SC disease (HbSC). A healthy control (HC) group of 59 individuals was also included. Hematological and biochemical analyses were carried out using electronic methods. TGF-β1, TIMP-1, and MMP-9 plasma quantifications were performed by ELISA. TGF-β1 plasma levels were higher in HbSS individuals than in HbSC and HC. In individuals with HbSS, TGF-β1 levels were positively correlated with red blood cells, hemoglobin, hematocrit, platelets, and TIMP-1. In addition, HbSS individuals with TGF-β1 levels above the median (≥72.29 ng/mL) also presented increased monocyte counts and decreased albumin levels. In patients with HbSC, TGF-β1 levels were positively correlated with leukocytes, eosinophils, lymphocytes, monocytes, and platelets, as well as levels of TIMP-1, VLDL-C, triglycerides, heme, and AST. Additionally, HbSC individuals with TGF-β1 levels above the median (≥47.80 ng/mL) presented increased leukocyte and platelet counts, as well as increased levels of triglycerides, VLDL-C, MMP-9, and TIMP-1, and decreased HDL-C. Our findings suggest that TGF-β1 may play important roles in vascular remodeling, vasculopathy, angiogenesis, and inflammation in pediatric patients with SCD