Whole blood transcriptomic analysis reveals PLSCR4 as a potential marker for vaso-occlusive crises in sickle cell disease

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.

Whole‐blood transcriptome analysis reveals distinct gene expression signatures in paediatric patients with sickle cell anaemia before and after exercise

“…This is in accordance with adult data reported by Abdulwahab et al, who found up-regulation of similar genes, particularly PLSCR4, whose functions could be implicated in erythrocyte adhesion, aggregation and vaso-occlusion. 6 Consistent with prior RNAseq research in paediatric populations, 7 our study identified gene pathways associated with changes in gas transport in paediatric SCA when compared to their healthy counterparts. Furthermore, within the two pathways examined in our study, we identified additional gene families that have previously been documented as up-regulated in the blood of paediatric patients with SCA.…”

“…Whole-blood transcriptome analysis reveals distinct gene expression signatures in paediatric patients with sickle cell anaemia before and after exercise Abel Plaza-Florido 1 | Robert I. Liem 2 | Fadia Haddad 1 | Shlomit Radom-Aizik 1 investigated in several studies using whole-blood transcriptome profiling. [6][7][8] Treatments for SCA often focus on managing inflammation as well as preventing and treating complications. Regular exercise can have many benefits for individuals with SCA, including improved cardiopulmonary fitness, and reduced pain and inflammation.…”

Evaluation of Current Clinical Research Spectrum of Sickle Cell Anemia to Approach New Innovative Developmental Techniques for Enhancing Sudanese Health Systems

“…PCR can distinguish recognized single genes or numerous genes in a solitary tube. Then, the result can be detected by gel electrophoresis, sequencing, melting curve analysis, or monitoring the change in the uorescence (35). For detection of mutation point or minor loss of DNA, the suitable technique is ampli cation-refractory mutation system (ARMS).…”

Treatment of sickle cell anemia using CRISPR and prime editing

“…After treatment, the patient's daily life is still troubled and the prognosis is still very limited. The average age of death for people with sickle cell anemia (homozygous sickle hemoglobin) is only over 40 years old [8].This shows that sickle cell disease is still a serious threat to human beings. Therefore, it is urgent to find a more effective treatment strategy.…”