Abstract
Sickle cell disease, a common genetic blood disorder, results from a point mutation in the β-globin gene affecting the configuration of hemoglobin, predisposing to painful vaso-occlusive crisis (VOC) and multi-organ dysfunctions. There is a huge variation in the phenotypic expressions of SCD and VOC owing to genetic and environmental factors. This study aimed to characterize the whole blood gene expression profile using Microarray technology in Bahraini patients with SCD determining the differentially expressed genes in steady-state (n = 10) and during VOC (n = 10) in comparison to healthy controls (n = 8). Additionally, the study intended to identify potential genetic marker associated with hemolysis. The analysis identified 2073 and 3363 genes that were dysregulated during steady-state and VOC, respectively, compared to healthy controls. Moreover, 1078 genes were differentially expressed during VOC compared to steady state. The PLSCR4 gene was almost 6-fold up-regulated in microarray, 4-fold in polymerase chain reaction, and a mean protein concentration of 0.856 ng/ml was observed in enzyme-linked immunosorbent assay during VOC compared to steady-state (0.238 ng/ml) (p < 0.01). Amongst these genes, PLSCR4 is involved in erythrocyte membrane deformity thus, predisposing to hemolysis, adhesion, and thrombosis. In conclusion, PLSCR4 may serve as a potential biomarker for VOC and future large-scale validation are recommended.
Highlights
Sickle cell disease, a common genetic blood disorder, results from a point mutation in the β-globin gene affecting the configuration of hemoglobin, predisposing to painful vaso-occlusive crisis (VOC) and multi-organ dysfunctions
Sickle cell disease (SCD) is a group of inherited blood disorders caused by a mutation in the hemoglobin gene that results in the formation of hemoglobin S (HbS) and leads to hemolytic anemia, painful attacks and multiple organ dysfunctions[1,2]
Male Female Age Mean in years ± standard deviation (SD) No of VOC per year ± SD White Blood Cell counts Mean in × 1 09/L ± SD Red Blood Cell counts Mean in × 1 012/L ± SD Mean corpuscular volume Mean in fL ± SD Mean corpuscular hemoglobin Mean in pg ± SD Hemoglobin Mean in g/dL ± SD Hematocrit Mean in % ± SD Platelet Mean in × 109/L ± SD Retics Mean in % ± SD Hemoglobin F Mean in % ± SD Hemoglobin S Mean in % ± SD Bilirubin mean in μmol/L ± SD Direct Indirect Lactate dehydrogenase Mean in U/L ± SD
Summary
A common genetic blood disorder, results from a point mutation in the β-globin gene affecting the configuration of hemoglobin, predisposing to painful vaso-occlusive crisis (VOC) and multi-organ dysfunctions. The PLSCR4 gene was almost 6-fold up-regulated in microarray, 4-fold in polymerase chain reaction, and a mean protein concentration of 0.856 ng/ml was observed in enzyme-linked immunosorbent assay during VOC compared to steady-state (0.238 ng/ ml) (p < 0.01). This study aimed to compare SCD patients using gene expression analysis by microarray to improve our knowledge of the disease pathophysiology and to detect genetic markers associated with the VOC.
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