Endothelin-1 gene polymorphisms (G8002A) and endothelial monocyte-activated peptide II: role in vascular dysfunction in pediatric β-thalassemia patients

Research Background:

Endothelin-1 (ET-1) is a potent endogenous vasoconstrictor that stimulates the production
of reactive oxygen species.
Endothelial monocyte-activated polypeptide-II (EMAP-II) is a versatile polypeptide
.


Research Objectives:

To assess the ET-1 gene polymorphism (G8002A) in pediatric patients with β-thalassaemia (β-TM) as a potential genetic marker for vascular dysfunction and its possible relationship
with EMAP-II, oxidative stress, and vascular complications.


Research Methods:

Patients with β-TM with asymptomatic heart or kidney disease (n = 95) were compared
to 95 healthy controls.
Measurement of hemolysis markers, serum ferritin, urine albumin-creatinine ratio, serum EMAP II, malondialdehyde (MDA), and antioxidant enzymes; Superoxide dismutase (SOD), glutathione peroxidase (GPx), reduced glutathione (GSH), glutathione reductase, and catalase
.
The polymorphism of the ET-1 gene (G8002A)
was determined by polymerase chain reaction-restriction fragment length polymorphism.


Research results:

Patients with β-TM had significantly higher EMAP II than healthy controls
.
EMAP II was significantly higher
in patients with heart disease, pulmonary hypertension (PH) risk, kidney disease, poor treatment adherence, and ferritin ≥ 2500 μg/L.
There was a significant correlation
between EMAP II and transfusion index, LDH, ferritin, and markers of oxidative stress.
The AA genotype of ET-1 gene polymorphism (G8002A) in patients with β-TM was significantly higher than that in the control group
.
Patients with the AA genotype had significantly more
heart disease, PH risk, or kidney disease than the GG and GA genotypes.
Lactate dehydrogenase (LDH), serum ferritin, EMAP II, MDA, SOD, and GPx were significantly higher
in the AA genotype.

Conclusions:

ET-1 gene polymorphisms (G8002A) may be a genetic marker
predicting increased susceptibility to cardiopulmonary and renal complications in pediatric β-TM patients.

References:

Tantawy AAG, Tadros MAR, Adly AAM, Ismail EAR, Ibrahim FA, Salah Eldin NM, Hussein MM, Alfeky MA, Ibrahim SM, Hashem MA, Ebeid FSE.
Endothelin-1 gene polymorphism (G8002A) and endothelial monocyte-activating polypeptide II: Role in vascular dysfunction in pediatric patients with β-thalassemia major.
Cytokine.
2022 Oct 21; 161:156048.
doi: 10.
1016/j.
cyto.
2022.
156048.
Epub ahead of print.
PMID: 36279697.