The endocannabinoid system's genetic polymorphisms in sickle cell anemia patients.

Sickle cell anemia (SCA) is a monogenic blood disease with complex and multifactorial pathophysiology. The endocannabinoid system (ECS) could be a candidate for modulating SCA complications, such as priapism, as it has demonstrated an essential role in hematopoiesis, platelet aggregation, and immune responses. We evaluated the association of ECS-related single nucleotide polymorphisms (SNP) (FAAH rs324420, MAGL rs604300, CNR1 rs7766029, and CNR2 rs35761398) with priapism in a Brazilian SCA cohort.

Association of HMIP1 C-893A polymorphism and disease severity in patients with sickle cell anemia.

Introduction: Sickle cell anemia (SCA) is a Mendelian disorder with a heterogeneous clinical course. The reasons for this phenotypic diversity are not entirely established, but it is known that high fetal hemoglobin levels lead to a milder course of the disease. Additionally, genetic variants in the intergenic region HBS1L-MYB promote high levels of fetal hemoglobin into adulthood.

Atypical β-S haplotypes: classification and genetic modulation in patients with sickle cell anemia.

β-S globin haplotype (β haplotype) characterization in sickle cell anemia (SCA) patients is important because it assists individualized treatment. However, the patient with atypical haplotypes do not present detailed studies such as clinical and laboratory data. To understand the phenotypic expression of atypical haplotype patients in relation to typical haplotype ones, it may be necessary to assess the main clinical and laboratorial parameters and investigate transcription factors, as possible genetic modulators that can contribute to the improvement of the SCA patients' clinical condition.

The relationship between of ACE I/D and the MTHFR C677T polymorphisms in the pathophysiology of type 2 diabetes mellitus in a population of Brazilian obese patients.

Objectives This study aimed to evaluate the frequencies of the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) and methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphisms in obese patients with and without type 2 diabetes mellitus (T2DM). Subjects and methods These polymorphisms were analyzed by polymerase chain reaction in 125 patients with obesity, 47 (T2DM) and 78 (Control Group). Results No significant difference was found on comparing the T2DM and Control Groups in respect to the genotypic frequencies of the polymorphisms - (II: 13.

Correction: Inflammation in Sickle Cell Disease: Differential and Down-Expressed Plasma Levels of Annexin A1 Protein.

[This corrects the article DOI: 10.1371/journal.pone.

Impact of genetic polymorphisms in key enzymes of homocysteine metabolism on the pathophysiology of sickle cell anemia.

This work aimed at studying a possible influence of methylenetetrahydrofolate reductase (MTHFR; c. 677C>T) and cystathionine β-synthase (CBS; 844ins68) polymorphisms on overall oxidative status of sickle cell anemia (SCA) patients and on routine markers, correlating them with hydroxycarbamide (HC) treatment. We evaluated 95 unrelated and diagnosed SCA patients.

Inflammation in Sickle Cell Disease: Differential and Down-Expressed Plasma Levels of Annexin A1 Protein.

Sickle cell disease (SCD) is an inherited hemolytic anemia whose pathophysiology is driven by polymerization of the hemoglobin S (Hb S), leading to hemolysis and vaso-occlusive events. Inflammation is a fundamental component in these processes and a continuous inflammatory stimulus can lead to tissue damages. Thus, pro-resolving pathways emerge in order to restore the homeostasis.

Phenotypic Diversity of Sickle Cell Disease in Patients with a Double Heterozygosity for Hb S and Hb D-Punjab.

Phenotypic heterogeneity for sickle cell disease is associated to several genetic factors such as genotype for sickle cell disease, β-globin gene cluster haplotypes and Hb F levels. The coinheritance of Hb S (HBB: c.20A > T) and Hb D-Punjab (HBB: c.

Hemoglobin (Hb) Val de Marne (Hb Footscray) in Brazil: the first case report.

Hemoglobin (Hb) variants involving alpha-chains are less common in the global population than Hb variants resulting from beta-chain alterations. Generally, alpha-chain Hb variants are caused by point mutations affecting alpha-1 and/or alpha-2 genes of the alpha-globin cluster (HBA1 and HBA2). In Brazil, the most prevalent alpha-chain Hb variant is Hb Hasharon.

Inheritance of the Bantu/Benin haplotype causes less severe hemolytic and oxidative stress in sickle cell anemia patients treated with hydroxycarbamide.

Beta S-globin gene cluster haplotypes (β(S)-haplotypes) can modulate the response to hydroxycarbamide (HC) treatment in sickle cell anemia (SCA) patients. In Brazil, the most common haplotypes are Bantu and Benin, and both confer a poor prognosis for patients when untreated with HC. We evaluated oxidative and hemolytic biomarkers in 48 SCA patients undergoing HC treatment separated in three subgroups: Bantu/Bantu, Bantu/Benin and Benin/Benin haplotype.

Plasma levels of TGF-β1 in homeostasis of the inflammation in sickle cell disease.

Sickle cell disease (SCD) represents a chronic inflammatory condition with complications triggered by the polymerization of hemoglobin S (Hb S), resulting in a series of cellular interactions mediated by inflammatory cytokines, as the transforming growth factor beta (TGF-β), which plays an important role in inflammation resolution. This study assessed the relation between SCD inflammation and the plasma concentration of TGF-β1, and also checked the influence of the presence of -509C/T polymorphism in TGFB1 gene on TGF-β1 plasma values. The plasma levels of TGF-β1 were quantified by ELISA in 115 patients with SCD (genotypes SS, SD-Los Angeles, Sβ-thalassemia and SC) and in 58 individuals with no hemoglobinopathies (Hb AA), as the control group.

Severity of Brazilian sickle cell disease patients: severity scores and feasibility of the Bayesian network model use.

The integration of the several clinical and laboratory dimensions and the influence of each parameter on the sickle cell disease (SCD)-related mortality is useful for predicting the phenotype of an individual. This study evaluated the feasibility of the SCD severity calculator use to measure disease severity in Brazilian patients. The study group was composed of 500 SCD patients (440 HbSS and 60 HbSC) diagnosed by molecular biology.

Frequencies of -308G/A (TNFA) and -509C/T (TGFB1) polymorphisms in sickle cell anemia patients from Brazil.

Sickle cell anemia is an affection that causes chronic inflammation, with consequences for vaso-occlusion, oxidative stress and cytokine production. Genetic polymorphisms in markers involved in this process can modulate the inflammatory response, including polymorphisms -308G/A of TNFA (tumor necrosis factor alpha) and -509C/T of TGFB1 (transforming growth factor beta 1), reported to increase TNF-α and TGF-β1 production, respectively. Changes in the cytokine balance are important risk factors for clinical events; consequently, we examined the frequencies of these polymorphisms in 240 Brazilian sickle cell anemia patients from southeast Brazil.

Influence of βS allele in the lipid peroxidation and antioxidant capacity parameters.

Introduction: The oxidative process plays a fundamental role in the pathophysiology of sickle cell anemia (SCA), and population and environmental characteristics may influence redox balance. The aim of this study was to evaluate lipid peroxidation and antioxidant capacity in Brazilian Hb S carriers undergoing different therapies.

Methods: Blood samples from 270 individuals were analyzed (Hb SS, n = 68; Hb AS, n = 53, and Hb AA, n = 149).

Oxidative stress in sickle cell disease: an overview of erythrocyte redox metabolism and current antioxidant therapeutic strategies.

Erythrocytes have an environment of continuous pro-oxidant generation due to the presence of hemoglobin (Hb), which represents an additional and quantitatively significant source of superoxide (O2(-)) generation in biological systems. To counteract oxidative stress, erythrocytes have a self-sustaining antioxidant defense system. Thus, red blood cells uniquely function to protect Hb via a selective barrier allowing gaseous and other ligand transport as well as providing antioxidant protection not only to themselves but also to other tissues and organs in the body.

The influence of hydroxyurea on oxidative stress in sickle cell anemia.

Objective: The oxidative stress in 20 sickle cell anemia patients taking hydroxyurea and 13 sickle cell anemia patients who did not take hydroxyurea was compared with a control group of 96 individuals without any hemoglobinopathy.

Methods: Oxidative stress was assessed by thiobarbituric acid reactive species production, the Trolox-equivalent antioxidant capacity and plasma glutathione levels.

Results: Thiobarbituric acid reactive species values were higher in patients without specific medication, followed by patients taking hydroxyurea and the Control Group (p < 0.

Oxidative stress and antioxidant capacity in sickle cell anaemia patients receiving different treatments and medications for different periods of time.

To evaluate, in a longitudinal study, the profile of lipid peroxidation and antioxidant capacity markers in sickle cell anaemia patients receiving different treatments and medication over different time periods. The three groups were: patients undergoing transfusion therapy and receiving iron chelator deferasirox (DFX group, n = 20); patients receiving deferasirox and hydroxyurea (DFX + HU group, n = 10), and patients receiving only folic acid (FA group, n = 15). Thiobarbituric acid-reactive substance (TBARS) assays and trolox-equivalent antioxidant capacity (TEAC) assays were evaluated during two different periods of analysis, T0 and T1 (after ~388 days).

Relationship between oxidative stress, glutathione S-transferase polymorphisms and hydroxyurea treatment in sickle cell anemia.

This study evaluated the oxidative stress and antioxidant capacity markers in sickle cell anemia (SCA) patients with and without treatment with hydroxyurea. We assessed GSTT1, GSTM1 and GSTP1 polymorphisms in patients and a control group. The study groups were composed of 48 subjects without hemoglobinopathies and 28 SCA patients, 13 treated with HU [SCA (+HU)], and 15 SCA patients not treated with HU [SCA (-HU)].

Serum melatonin level and oxidative stress in sickle cell anemia.

This study evaluated serum melatonin levels in patients with sickle cell anemia (SCA) and compared the results to lipid peroxidation by determining thiobarbituric acid-reactive substances (TBARS) and Trolox equivalent antioxidant capacity (TEAC). The group studied was composed of 15 SCA patients and 24 subjects without hemoglobinopathies. The average melatonin level was significantly reduced in the SCA patients (p<0.

The XmnI polymorphic site 5' to the gene G(γ) in a Brazilian patient with sickle cell anaemia - fetal haemoglobin concentration, haematology and clinical features.

We report a 20-year-old female with sickle cell anaemia and with an HbF concentration of 15.8%. The patient was not using hydroxyurea and was not receiving regular blood transfusions.