Current Issues in Molecular Biology (Jun 2022)

Molecular Determination of Vascular Endothelial Growth Factor, miRNA-423 Gene Abnormalities by Utilizing ARMS-PCR and Their Association with Fetal Hemoglobin Expression in the Patients with Sickle Cell Disease

  • Abdullah Hamadi,
  • Rashid Mir,
  • Ali Mahzari,
  • Abdulrahim Hakami,
  • Reema Almotairi,
  • Gasim Dobie,
  • Fawaz Hamdi,
  • Mohammed Hassan Nahari,
  • Razan Alhefzi,
  • Mohammed Alasseiri,
  • Nora Y. Hakami,
  • Hadeel Al Sadoun,
  • Osama M. Al-Amer,
  • Jameel Barnawi,
  • Hassan A. Madkhali

DOI
https://doi.org/10.3390/cimb44060175
Journal volume & issue
Vol. 44, no. 6
pp. 2569 – 2582

Abstract

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Recent studies have indicated that microRNA and VEGF are considered to be genetic modifiers and are associated with elevated levels of fetal haemoglobin HbF, and thus they reduce the clinical impact of sickle haemoglobin (HbS) patients. This cross-sectional study was performed on clinical confirmed subjects of SCD cases. miR-423-rs6505162 C>T and VEGF-2578 C>A genotyping was conducted by ARMS-PCR in SCD and healthy controls. A strong clinical significance was reported while comparing the association of miR-423 C>T genotypes between SCD patients and controls (p = 0.031). The microRNA-423 AA genotype was associated with an increased severity of SCD in codominant model with odd ratio (OR = 2.36, 95% CI, (1.15–4.84), p = 0.018) and similarly a significant association was observed in recessive inheritance model for microRNA-423 AA vs (CC+CA) genotypes (OR = 2.19, 95% CI, (1.32–3.62), p p A genotypes between SCD patients and healthy controls was significant (p p SCD patients carrying miR-423 CA genotype HbA1 (59.98%), HbA2 (3.74%) whereas SCD patients carrying miR-423 CA genotype has higher expression of HbF (0.98%) and HbS (38.1%) than in the patients carrying AA genotype HbF (0.60%), HbS (36.1%). ARMS-PCR has been proven to be rapid, inexpensive and is highly applicable to gene mutation screening in laboratories and clinical practices. This research highlights the significance of elucidating genetic determinants that play roles in the amelioration of the HbF levels that is used as an indicator of severity of clinical complications of the monogenic disease. Further well-designed studies with larger sample sizes are necessary to confirm our findings.

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