Association of FOXO3 polymorphism (rs3800231) and clinical subphenotypes of beta thalassemic individuals

• Published in: Hematology, Transfusion and Cell Therapy Vol. 44; no. 2; pp. 156 - 162
• Main Authors: Torres, Flaviene F, Bernardo, Victoria S, Silva, Danilo G H, Okumura, Jéssika V, Bonini-Domingos, Claudia R
• Format: Journal Article
• Language: English
• Published: Brazil Sociedade Brasileira de Hematologia e Hemoterapia 01-04-2022; Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular (ABHH); Elsevier
• Subjects: Clinical manifestations; Forkhead box O; Genetic polymorphism; MEDICINE, GENERAL & INTERNAL; Original; Clinical manifestations; Forkhead box O; Genetic polymorphism
• ISSN: 2531-1379; 2531-1387; 2531-1387
• DOI: 10.1016/j.htct.2020.09.147

Studies have shown that the loss of the FOXO3 transcriptional function is involved in the pathophysiology of some chronic erythroid disorders, including beta-thalassemia (β-thal). Therefore, the single nucleotide polymorphism (SNP) rs3800231 (35-2764A > G) could contribute to alterations in its transcriptional activity, acting as a modifier of β-thal phenotypic manifestations.
In order to better understand the genotypic and/or allelic distributions among β-thal patients, we evaluated 83 β-thal heterozygous and 20 homozygous, compared to 117 individuals without hemoglobinopathies (control group). Additionally, we verified any influence of the FOXO3 polymorphism on clinical manifestations among β-thal homozygotes.
We obtained higher frequencies of the wild-type homozygous (AA) and the wild-type allele (A) in the β-thal group (p < 0.0001 and p = 0.00014, respectively). The most common clinical manifestations found among β-thal homozygotes were iron overload (90%), splenomegaly (65%) and bone complications (35%), e.g., osteopenia/osteoporosis. We observed that close to 80% of the patients presenting such manifestations had the genotype AA. However, we did not find any significant involvement of the FOXO3 polymorphism in clinical manifestation occurrences.
Thus, we concluded that the SNP rs3800231 did not play a significant role as a modifier of the clinical manifestations observed in the β-thal homozygotes studied.