Genetic variation in FOXP3 and ROR-γ genes in pediatric acute lymphocytic leukemia (ALL) patients: correlation with associated cytokines

Eman A El-Maadawy; Rania M Bakry; Mohamed M Moussa; Sobhy Hasab El-Naby; Roba M Talaat

doi:10.1007/s12672-022-00549-3

Genetic variation in FOXP3 and ROR-γ genes in pediatric acute lymphocytic leukemia (ALL) patients: correlation with associated cytokines

Discov Oncol. 2022 Sep 9;13(1):86. doi: 10.1007/s12672-022-00549-3.

Authors

Eman A El-Maadawy¹, Rania M Bakry², Mohamed M Moussa³, Sobhy Hasab El-Naby⁴, Roba M Talaat⁵

Affiliations

¹ Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI], University of Sadat City, El Sadat City, Egypt.
² South Egypt Cancer Institute, Assiut University, Assiut, Egypt.
³ Clinical Hematology and Bone Marrow Transplantation, Ain-Shams University, Cairo, Egypt.
⁴ Zoology Department, Faculty of Science, Menoufiya University, Menoufiya, Egypt.
⁵ Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI], University of Sadat City, El Sadat City, Egypt. roba.talaat@gebri.usc.edu.eg.

Abstract

Background: FOXP3 and ROR-γ genes are master regulators of the Treg and Th17 differentiation, respectively. This work was planned to investigate the impact of FOXP3 (rs3761548C/A and rs3761549C/T) and ROR-γ (rs9017A/G & rs9826A/G) gene polymorphism on the vulnerability of pediatric Egyptians to acute lymphoblastic leukemia (ALL). Furthermore, we evaluated the impact of these genetic variations on Treg/Th17-related cytokines.

Methods: FOXP3 SNPs were genotyped using PCR-based restriction fragment length polymorphism (PCR-RFLP), while ROR-γ SNPs polymorphism were performed by PCR-sequence-specific primer (PCR-SSP). An Enzyme-linked immunosorbent assay (ELISA) was used to assess the levels of Treg/Th17 associated cytokines on 128 ALL children and 124 healthy donors.

Results: Compared to controls, patients had a significant increase (p < 0.01/p < 0.05) in FOXP3rs3761548CC genotype and a significant decrease (p < 0.001/p < 0.01) inrs3761548CA genotype. A significant elevation (p < 0.001/p < 0.01) in ROR-γ rs9017AA genotype and a significant reduction (p < 0.01/p < 0.05) in rs9017AG genotype were detected in ALL patients versus controls. An insignificant change in FOXP3 (rs3761549C/T) and ROR-γ (rs9826A/G) genotypes was demonstrated between both groups. ROR-γ GG and GA haplotypes were significantly decreased (p < 0.05/p < 0.05; p < 0.05/p < 0.05) in ALL subjects compared to healthy ones. Relapsed patients had a significantly higher (p < 0.05/P < 0.05) frequency of FOXP3 rs3761548CA genotype than non-relapsed subjects. ROR-γ rs9017AG and rs9826GG genotypes might be associated with the increase in IL-23 plasma level.

Conclusions: Our preliminary data provided evidence for the impact ofFOXP3 (rs3761548C/A) and ROR-γ (rs9017A/G) gene polymorphisms and the occurrence of ALL in Egyptian children. Another large-scale prospective study should be conducted to validate these findings.

Keywords: Cytokines; FOXP3; Pediatric ALL; ROR-γ; SNPs; Treg/Th17 cells.