Department of Immunology, Medical School, Shiraz University of Medical Sciences, Shiraz, 71345-1798, Iran.
Autoimmune Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, 71345-1798, Iran.
Mol Biol Rep. 2021 Feb;48(2):1139-1150. doi: 10.1007/s11033-021-06154-x. Epub 2021 Jan 30.
FOXP3 X-linked gene has crucial roles in the development and function of regulatory T cells. We investigated the association of FOXP3 rs3761548, rs3761549 and rs2294021 single nucleotide polymorphisms (SNPs) with acute lymphoblastic leukemia (ALL) susceptibility and response to therapy. Genotyping was performed in 247 patients and 210 healthy subjects. We observed a higher frequency of rs3761548 A carriers and rs2294021 C carriers (p < 0.04) in male patients, and lower frequencies of rs3761548 AC genotype (p = 0.04) and rs2294021 CT genotype (p = 0.01) in female patients compared to controls. ACC (p = 0.04) and ATC haplotypes (p = 0.002) were associated with susceptibility to ALL. There was a significant correlation between the genotypes of rs3761548 and rs2294021 SNPs with event-free survival (EFS) and overall survival (OS). The rs3761548 A genotype in male patients was associated with increased risk of relapse (p < 0.0001), shorter EFS, increased death rate (p = 0.002) and shorter OS compared to C genotype (p = 0.001). Similar significant results were observed for the relation of rs2294021 C genotype with response to therapy in male patients. In females, patients with rs3761548 AC genotype had longer EFS (p = 0.02) and those with rs2294021 CT had longer EFS and OS (p < 0.005). According to haplotype analysis, patients carrying ACC or ATC haplotypes had the highest number of WBCs and shorter EFS or OS, and patients with CCT haplotype had the lowest number of WBCs and longer EFS or OS. These results provided evidence for the impact of these polymorphisms on susceptibility and response to therapy in children with ALL.
叉头框蛋白 P3 (FOXP3)X 连锁基因在调节性 T 细胞的发育和功能中具有关键作用。我们研究了 FOXP3 rs3761548、rs3761549 和 rs2294021 单核苷酸多态性 (SNP) 与急性淋巴细胞白血病 (ALL) 易感性和对治疗的反应之间的关系。对 247 例患者和 210 例健康对照进行了基因分型。我们观察到男性患者中 rs3761548A 携带者和 rs2294021C 携带者的频率较高（p < 0.04），女性患者中 rs3761548AC 基因型（p = 0.04）和 rs2294021CT 基因型（p = 0.01）的频率较低。ACC（p = 0.04）和 ATC 单倍型（p = 0.002）与 ALL 的易感性相关。rs3761548 和 rs2294021 SNP 基因型与无事件生存（EFS）和总生存（OS）显著相关。男性患者中 rs3761548A 基因型与复发风险增加相关（p < 0.0001），EFS 更短，死亡率增加（p = 0.002），OS 更短，与 C 基因型相比（p = 0.001）。在男性患者中，rs2294021C 基因型与治疗反应的关系也观察到了类似的显著结果。在女性中，rs3761548AC 基因型患者的 EFS 较长（p = 0.02），rs2294021CT 基因型患者的 EFS 和 OS 较长（p < 0.005）。根据单倍型分析，携带 ACC 或 ATC 单倍型的患者白细胞数最高，EFS 或 OS 较短，而携带 CCT 单倍型的患者白细胞数最低，EFS 或 OS 较长。这些结果为这些多态性对儿童 ALL 易感性和对治疗的反应的影响提供了证据。
