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

• Main Author: Torres, Flaviene F. [UNESP]
• Publication Date: 2020
• Other Authors: Bernardo, Victoria S. [UNESP], Silva, Danilo G.H. [UNESP], Okumura, Jéssika V., Bonini-Domingos, Claudia R. [UNESP]
• Format: Article
• Language: eng
• Source: Repositório Institucional da UNESP
• Download full: http://dx.doi.org/10.1016/j.htct.2020.09.147; http://hdl.handle.net/11449/208251
• topic: Clinical manifestations; Forkhead box O; Genetic polymorphism

Introduction: 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. Objective and method: 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. Results: 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. Conclusion: 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.