The exploring of growth differentiation factor-15 and H63D gene polymorphisms in β-thalassemia major: Implications for cardiovascular risk and iron overload

Abstract

BACKGROUND: β-thalassemia major (βTM) is a genetic disorder characterized by a deficiency in hemoglobin production, ineffective erythropoiesis, chronic hemolysis, lifelong blood transfusions, iron overload, and increased risk of cardiac complications. OBJECTIVE: The study aimed to evaluate the growth differentiation factor-15 (GDF-15) concentration in βTM patients and its correlation with cardiac complications. H63D refers to a specific mutation in the HFE gene, which is associated with hereditary hemochromatosis (HH), a genetic disorder characterized by excessive accumulation of iron in the body. This mutation involves a change of histidine (H) to aspartic acid (D) at position 63 in the HFE protein. This mutation is often only written abbreviated as (H63D). MATERIALS AND METHODS: This case–control study was done on 120 subjects. A total of 60 patient samples were randomly collected from the Genetic Hematology Center at the Babylon Hospital, with an age range of 10–26 years. In addition, 60 samples were collected from healthy children in the same age range as the control group; patients and controls were subdivided into (10–18) and (18–26) year groups. GDF-15 was measured by enzyme-linked immunosorbent assay, and the genotyping of mutation was done by amplification refractory mutation system-polymerase chain reaction technique. RESULTS: The study revealed a significant increase in ferritin (FER) and GDF-15 levels in the patients compared to controls (P < 0.001). GDF-15 showed a direct correlation with age (r = 0.244, P = 0.02) and FER (r = 0.215, P = 0.04). There was a significant difference in H63D mutations between controls and patients (P = 0.044), with a higher proportion of the C-G (heterozygous for the mutant allele) genotype observed in βTM patients (31.67%). Additionally, a notable effect of the H63D mutation on serum ferritin (higher) levels within the βTM group was observed. CONCLUSION: Elevations of the GDF-15 in βTM patients indicate a high risk of cardiovascular complications in patients with βTM. The H63D mutation of the hemostatic iron regulator (HFE) gene is frequently found in βTM. Although a significant effect of the mutation was obtained on serum FER levels, it did not act as a risk factor in βTM patients. However, the frequent presence of the H63D mutation in patients indicated a possible association between single-nucleotide polymorphism and the iron regulation pathway.

Keywords

• beta-thalassemia major
• cardiac complication
• growth differentiation factor-15
• h63d
• hfe