Whole Blood Transcriptomic Analysis of Sickle Cell Trait

Area of Science:

• Genomics
• Hematology
• Molecular Biology

Background:

• Sickle cell trait (SCT) is the carrier state for the sickle cell disease (SCD) gene.
• SCT is associated with increased risks of venous thromboembolism and chronic kidney disease.
• Previous studies suggest SCT alters clinical laboratory parameters.

Purpose of the Study:

• To investigate differential gene expression in individuals with SCT compared to non-carriers.
• To identify specific genes and pathways affected by SCT.
• To explore potential mechanisms linking SCT to adverse health outcomes.

Main Methods:

• RNA sequencing was performed on whole blood samples from 805 African American women (143 SCT, 660 controls).
• Differential gene expression analysis was conducted to identify genes with significant expression changes in SCT.
• Pathway enrichment analysis was used to determine biological processes affected by SCT.

Main Results:

• 226 differentially expressed genes (DEGs) were identified in SCT compared to controls (FDR < 0.05).
• Enriched pathways included erythropoiesis, hemoglobin synthesis, and proteasomal degradation.
• SCT-associated DEGs showed patterns similar to those in SCD, including upregulated ubiquitin-related genes.

Conclusions:

• SCT is associated with significant differential gene expression in whole blood.
• The identified DEGs and pathways suggest potential links between SCT, hemolysis, erythropoiesis, and kidney injury.
• Further research, including single-cell transcriptomics, is warranted to elucidate SCT's mechanisms for adverse health outcomes.