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  • Title: The role of FOXP3 rs3761548 and rs2294021 polymorphisms in pediatrics acute lymphoblastic leukemia: association with risk and response to therapy.
    Author: Ghasemi Z, Kalantar K, Amirghofran Z.
    Journal: Mol Biol Rep; 2021 Feb; 48(2):1139-1150. PubMed ID: 33517519.
    Abstract:
    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.
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