Genetic variation in FOXP3 and ROR-γ genes in pediatric acute lymphocytic leukemia (ALL) patients: correlation with associated cytokines
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 Egypt...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Springer
2022-09-01
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| Series: | Discover Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1007/s12672-022-00549-3 |
| _version_ | 1811211590468370432 |
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| author | Eman A. El-maadawy Rania M. Bakry Mohamed M. Moussa Sobhy Hasab El-Naby Roba M. Talaat |
| author_facet | Eman A. El-maadawy Rania M. Bakry Mohamed M. Moussa Sobhy Hasab El-Naby Roba M. Talaat |
| author_sort | Eman A. El-maadawy |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T05:15:20Z |
| format | Article |
| id | doaj.art-ed36be5836ee4e3db79d73596a689e71 |
| institution | Directory Open Access Journal |
| issn | 2730-6011 |
| language | English |
| last_indexed | 2024-04-12T05:15:20Z |
| publishDate | 2022-09-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj.art-ed36be5836ee4e3db79d73596a689e712022-12-22T03:46:38ZengSpringerDiscover Oncology2730-60112022-09-0113111610.1007/s12672-022-00549-3Genetic variation in FOXP3 and ROR-γ genes in pediatric acute lymphocytic leukemia (ALL) patients: correlation with associated cytokinesEman A. El-maadawy0Rania M. Bakry1Mohamed M. Moussa2Sobhy Hasab El-Naby3Roba M. Talaat4Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI], University of Sadat CitySouth Egypt Cancer Institute, Assiut UniversityClinical Hematology and Bone Marrow Transplantation, Ain-Shams UniversityZoology Department, Faculty of Science, Menoufiya UniversityMolecular Biology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI], University of Sadat CityAbstract 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.https://doi.org/10.1007/s12672-022-00549-3Pediatric ALLFOXP3ROR-γSNPsCytokinesTreg/Th17 cells |
| spellingShingle | Eman A. El-maadawy Rania M. Bakry Mohamed M. Moussa Sobhy Hasab El-Naby Roba M. Talaat Genetic variation in FOXP3 and ROR-γ genes in pediatric acute lymphocytic leukemia (ALL) patients: correlation with associated cytokines Discover Oncology Pediatric ALL FOXP3 ROR-γ SNPs Cytokines Treg/Th17 cells |
| title | Genetic variation in FOXP3 and ROR-γ genes in pediatric acute lymphocytic leukemia (ALL) patients: correlation with associated cytokines |
| title_full | Genetic variation in FOXP3 and ROR-γ genes in pediatric acute lymphocytic leukemia (ALL) patients: correlation with associated cytokines |
| title_fullStr | Genetic variation in FOXP3 and ROR-γ genes in pediatric acute lymphocytic leukemia (ALL) patients: correlation with associated cytokines |
| title_full_unstemmed | Genetic variation in FOXP3 and ROR-γ genes in pediatric acute lymphocytic leukemia (ALL) patients: correlation with associated cytokines |
| title_short | Genetic variation in FOXP3 and ROR-γ genes in pediatric acute lymphocytic leukemia (ALL) patients: correlation with associated cytokines |
| title_sort | genetic variation in foxp3 and ror γ genes in pediatric acute lymphocytic leukemia all patients correlation with associated cytokines |
| topic | Pediatric ALL FOXP3 ROR-γ SNPs Cytokines Treg/Th17 cells |
| url | https://doi.org/10.1007/s12672-022-00549-3 |
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