El-Maadawy Eman A, Bakry Rania M, Moussa Mohamed M, El-Naby Sobhy Hasab, Talaat Roba M
Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI], University of Sadat City, El Sadat City, Egypt.
South Egypt Cancer Institute, Assiut University, Assiut, Egypt.
Discov Oncol. 2022 Sep 9;13(1):86. doi: 10.1007/s12672-022-00549-3.
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.
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.
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.
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.
FOXP3和ROR-γ基因分别是调节性T细胞（Treg）和辅助性T细胞17（Th17）分化的主要调控因子。本研究旨在探讨FOXP3（rs3761548C/A和rs3761549C/T）及ROR-γ（rs9017A/G和rs9826A/G）基因多态性对埃及儿童急性淋巴细胞白血病（ALL）易感性的影响。此外，我们评估了这些基因变异对Treg/Th17相关细胞因子的影响。
采用基于聚合酶链反应的限制性片段长度多态性（PCR-RFLP）技术对FOXP3单核苷酸多态性（SNP）进行基因分型，而ROR-γ SNP多态性通过PCR序列特异性引物（PCR-SSP）进行检测。采用酶联免疫吸附测定（ELISA）法评估128例ALL患儿和124例健康供者体内Treg/Th17相关细胞因子的水平。
与对照组相比，患者中FOXP3 rs3761548CC基因型显著增加（p<0.01/p<0.05），rs3761548CA基因型显著降低（p<0.001/p<0.01）。ALL患者与对照组相比，ROR-γ rs9017AA基因型显著升高（p<0.001/p<0.01），rs9017AG基因型显著降低（p<0.01/p<0.05）。两组间FOXP3（rs3761549C/T）和ROR-γ（rs9826A/G）基因型无显著变化。与健康受试者相比，ALL受试者中ROR-γ GG和GA单倍型显著降低（p<0.05/p<0.05；p<0.05/p<0.05）。复发患者中FOXP3 rs3761548CA基因型的频率显著高于未复发患者（p<0.05/P<0.05）。ROR-γ rs9017AG和rs9826GG基因型可能与血浆白细胞介素-23水平升高有关。
我们的初步数据为FOXP3（rs3761548C/A）和ROR-γ（rs9017A/G）基因多态性与埃及儿童ALL发病之间的关联提供了证据。应开展另一项大规模前瞻性研究以验证这些发现。
