scholarly journals THE EFFECT OF ALPHA THALASSEMIA, HBF and HBC ON HAEMATOLOGICAL PARAMETERS OF SICKLE CELL DISEASE PATIENTS IN IBADAN, NIGERIA.

2022 ◽  
Vol 14 (1) ◽  
pp. e2022001
Author(s):  
FASOLA ATINUKE
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
High Performance ◽  
Hematological Parameters ◽  
Globin Gene ◽  
Health Centre ◽  
Full Blood Count ◽  
Cell Disease ◽  
Alpha Thalassemia ◽  
Alpha Gene

Background: Sickle cell disease is a protean disease with limited data on the phenotypic and genetic variants in Nigeria. This study was conducted to provide baseline data on these variants by characterizing the existing forms of sickle cell disease and correlating these with basic hematological parameters. Methods: Adult and pediatric patients with SCD were recruited from a tertiary health centre in Nigeria. Patients were age and sex matched with healthy controls. Blood samples were obtained for Full Blood Count, phenotyping by High Performance Liquid Chromatography and genotyping for alpha thalassemia by multiplex gap polymerase chain reaction. Data analysis was done using IBM SPSS statistics version 23. Results: A total of 130 patients with sickle cell disease and 117 controls were studied. Alpha thalassemia in the study population was due to a 3.7kb deletion in the alpha globin gene cluster at a prevalence of 45.4% in the patients and 47% in controls. The prevalence of the various existing forms of SCD genotype was: Homozygous S without alpha gene deletion (HbSS)- 39.2%; HbSC - 10.8%; HbSα+1- 35.4%; HbSα+2 - 6.9% and HbSF- 7.7%. HbA2 was significantly elevated in individuals with two alpha gene deletions (HbSα+2). HbF and HbA2 were negatively correlated with each other (r= -0.587, p < 0.001). Individuals with the HbSC genotype followed by HbSα+2 had the best hematological parameters. Conclusions: Hematological parameters varied with hemoglobin genotype. The C hemoglobin and homozygous alpha thalassemia deletion had better ameliorating effect on SCD hematological parameters than the F hemoglobin in this population.  

scholarly journals The molecular basis of alpha thalassemia in India. Its interaction with the sickle cell gene

Blood ◽  
1988 ◽  
Vol 71 (2) ◽  
pp. 467-472 ◽  
Author(s):  
AE Kulozik ◽  
BC Kar ◽  
GR Serjeant ◽  
BE Serjeant ◽  
DJ Weatherall
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Globin Gene ◽  
Cell Disease ◽  
Alpha Thalassemia ◽  
Alpha Globin ◽  
Flanking Sequences ◽  
Cell Gene ◽  
Advantageous Effect ◽  
Genotype A

Abstract The alpha globin genotype of a total of 282 Indians from Orissa state has been analyzed. The overall alpha thalassemia gene frequency is 0.29, most frequently caused by the -alpha 3.7 and -alpha 4.2 deletions. In one family a novel -alpha 3.5 deletion removing the alpha 1 globin gene with some of its flanking sequences has been found, suggesting further sequence homology of the alpha globin gene cluster 3′ to the alpha 1 globin gene. Patients with sickle cell disease and alpha thalassemia had higher hemoglobin (Hb) levels, RBC counts, and Hb A2 levels, and lower reticulocyte counts, MCV, MCH, and Hb F levels than those with a normal alpha genotype. The frequency of splenomegaly was not influenced by the alpha globin genotype. A higher prevalence of alpha thalassemia was found in patients greater than or equal to 10 years of age than in the younger group, suggesting a possible advantageous effect of alpha thalassemia on the survival of patients with sickle cell disease.

Compound heterozygosity Hb S/Hb Hope (β136Gly→Asp): a pitfall in the newborn screening for sickle cell disease

1998 ◽  
Vol 5 (1) ◽  
pp. 27-30 ◽  
Author(s):  
R Ducrocq ◽  
A Bévier ◽  
A Leneveu ◽  
J Elion ◽  
M Maier-Redelsperger ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
High Performance ◽  
Globin Gene ◽  
Cell Disease ◽  
Analytical Strategy ◽  
Screening Strategies ◽  
Analytical Strategies ◽  
Hb S ◽  
Blood Specimens

The presence of Hb Hope associated with Hb S may represent a pitfall (false positive) in the neonatal detection of sickle cell disease by two of the most widely used analytical methods in screening programmes—isoelectric focusing (IEF) and high performance liquid chromatography (HPLC). This example illustrates the need to improve analytical strategies to avoid unnecessary anxiety and summoning of families often from a cultural background in which testing of the father is difficult to obtain. It is suggested that using two independent HPLC procedures might improve the specificity of the screening strategies. Additionally, simple procedures for detection of the most common mutations of the β globin gene on DNA extracted from dried blood specimens could be easily developed for the control of abnormal samples. These procedures could be introduced into the analytical strategy.

scholarly journals The molecular basis of alpha thalassemia in India. Its interaction with the sickle cell gene

Blood ◽  
1988 ◽  
Vol 71 (2) ◽  
pp. 467-472
Author(s):  
AE Kulozik ◽  
BC Kar ◽  
GR Serjeant ◽  
BE Serjeant ◽  
DJ Weatherall
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Globin Gene ◽  
Cell Disease ◽  
Alpha Thalassemia ◽  
Alpha Globin ◽  
Flanking Sequences ◽  
Cell Gene ◽  
Advantageous Effect ◽  
Genotype A

The alpha globin genotype of a total of 282 Indians from Orissa state has been analyzed. The overall alpha thalassemia gene frequency is 0.29, most frequently caused by the -alpha 3.7 and -alpha 4.2 deletions. In one family a novel -alpha 3.5 deletion removing the alpha 1 globin gene with some of its flanking sequences has been found, suggesting further sequence homology of the alpha globin gene cluster 3′ to the alpha 1 globin gene. Patients with sickle cell disease and alpha thalassemia had higher hemoglobin (Hb) levels, RBC counts, and Hb A2 levels, and lower reticulocyte counts, MCV, MCH, and Hb F levels than those with a normal alpha genotype. The frequency of splenomegaly was not influenced by the alpha globin genotype. A higher prevalence of alpha thalassemia was found in patients greater than or equal to 10 years of age than in the younger group, suggesting a possible advantageous effect of alpha thalassemia on the survival of patients with sickle cell disease.

Rapid and reliable β-globin gene cluster haplotyping of sickle cell disease patients by FRET Light Cycler and HRM assays

2011 ◽  
Vol 412 (13-14) ◽  
pp. 1257-1261 ◽  
Author(s):  
Philippe Joly ◽  
Philippe Lacan ◽  
Caroline Garcia ◽  
Angelique Delasaux ◽  
Alain Francina
Keyword(s):  
Sickle Cell Disease ◽  
Gene Cluster ◽  
Sickle Cell ◽  
Globin Gene ◽  
Cell Disease ◽  
Globin Gene Cluster ◽  
Light Cycler

scholarly journals 3,3′,5-Triiodothyroacetic acid (TRIAC) induces embryonic ζ-globin expression via thyroid hormone receptor α

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Huiqiao Chen ◽  
Zixuan Wang ◽  
Shanhe Yu ◽  
Xiao Han ◽  
Yun Deng ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Globin Gene ◽  
Erythroid Cells ◽  
Cell Disease ◽  
Potent Inducer ◽  
Thyroid Hormone Receptor Α

AbstractThe human ζ-globin gene (HBZ) is transcribed in primitive erythroid cells only during the embryonic stages of development. Reactivation of this embryonic globin synthesis would likely alleviate symptoms both in α-thalassemia and sickle-cell disease. However, the molecular mechanisms controlling ζ-globin expression have remained largely undefined. Moreover, the pharmacologic agent capable of inducing ζ-globin production is currently unavailable. Here, we show that TRIAC, a bioactive thyroid hormone metabolite, significantly induced ζ-globin gene expression during zebrafish embryogenesis. The induction of ζ-globin expression by TRIAC was also observed in human K562 erythroleukemia cell line and primary erythroid cells. Thyroid hormone receptor α (THRA) deficiency abolished the ζ-globin-inducing effect of TRIAC. Furthermore, THRA could directly bind to the distal enhancer regulatory element to regulate ζ-globin expression. Our study provides the first evidence that TRIAC acts as a potent inducer of ζ-globin expression, which might serve as a new potential therapeutic option for patients with severe α-thalassemia or sickle-cell disease.

scholarly journals Sickle Cell Disease: Role of Oxidative Stress and Antioxidant Therapy

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 296
Author(s):  
Rosa Vona ◽  
Nadia Maria Sposi ◽  
Lorenza Mattia ◽  
Lucrezia Gambardella ◽  
Elisabetta Straface ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Globin Gene ◽  
Organ Damage ◽  
Cell Disease ◽  
Vessel Occlusion ◽  
Antioxidant Agents ◽  
Oxidant Status

Sickle cell disease (SCD) is the most common hereditary disorder of hemoglobin (Hb), which affects approximately a million people worldwide. It is characterized by a single nucleotide substitution in the β-globin gene, leading to the production of abnormal sickle hemoglobin (HbS) with multi-system consequences. HbS polymerization is the primary event in SCD. Repeated polymerization and depolymerization of Hb causes oxidative stress that plays a key role in the pathophysiology of hemolysis, vessel occlusion and the following organ damage in sickle cell patients. For this reason, reactive oxidizing species and the (end)-products of their oxidative reactions have been proposed as markers of both tissue pro-oxidant status and disease severity. Although more studies are needed to clarify their role, antioxidant agents have been shown to be effective in reducing pathological consequences of the disease by preventing oxidative damage in SCD, i.e., by decreasing the oxidant formation or repairing the induced damage. An improved understanding of oxidative stress will lead to targeted antioxidant therapies that should prevent or delay the development of organ complications in this patient population.

Hypoxia-induced acute lung injury in murine models of sickle cell disease

2004 ◽  
Vol 286 (4) ◽  
pp. L705-L714 ◽  
Author(s):  
Kirkwood A. Pritchard ◽  
Jingsong Ou ◽  
Zhijun Ou ◽  
Yang Shi ◽  
James P. Franciosi ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Lung Injury ◽  
Sickle Cell ◽  
Globin Gene ◽  
Heat Shock Protein 90 ◽  
Cell Disease ◽  
Vascular Congestion ◽  
Nitrite Nitrate ◽  
Endothelial Nitric Oxide

Vaso-occlusive events are the major source of morbidity and mortality in sickle cell disease (SCD); however, the pathogenic mechanisms driving these events remain unclear. Using hypoxia to induce pulmonary injury, we investigated mechanisms by which sickle hemoglobin increases susceptibility to lung injury in a murine model of SCD, where mice either exclusively express the human α/sickle β-globin (hαβS) transgene (SCD mice) or are heterozygous for the normal murine β-globin gene and express the hαβStransgene (mβ+/-, hαβS+/-; heterozygote SCD mice). Under normoxia, lungs from the SCD mice contained higher levels of xanthine oxidase (XO), nitrotyrosine, and cGMP than controls (C57BL/6 mice). Hypoxia increased XO and nitrotyrosine and decreased cGMP content in the lungs of all mice. After hypoxia, vascular congestion was increased in lungs with a greater content of XO and nitrotyrosine. Under normoxia, the association of heat shock protein 90 (HSP90) with endothelial nitric oxide synthase (eNOS) in lungs of SCD and heterozygote SCD mice was decreased compared with the levels of association in lungs of controls. Hypoxia further decreased association of HSP90 with eNOS in lungs of SCD and heterozygote SCD mice, but not in the control lungs. Pretreatment of rat pulmonary microvascular endothelial cells in vitro with xanthine/XO decreased A-23187-stimulated nitrite + nitrate production and HSP90 interactions with eNOS. These data support the hypotheses that hypoxia increases XO release from ischemic tissues and that the local increase in XO-induced oxidative stress can then inhibit HSP90 interactions with eNOS, decreasing ·NO generation and predisposing the lung to vaso-occlusion.

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