Department of Hematology, Binzhou Medical University Hospital, Binzhou, China.
Eur Rev Med Pharmacol Sci. 2020 Aug;24(15):8048-8056. doi: 10.26355/eurrev_202008_22488.
The aim of this study was to investigate the correlations between interleukin-6 (IL-6) and IL-10 gene polymorphisms with childhood acute lymphoblastic leukemia.
Specimens were collected from 200 children with acute lymphoblastic leukemia (disease group) and 200 normal children (control group) in our hospital. DNA was extracted from peripheral blood nucleated cells in both groups to detect the gene polymorphisms rs2069830 and rs2069836 of IL-6, as well as rs3024489 and rs3024493 of IL-10. Then, the content of serum IL-6 and IL-10 was determined via enzyme-linked immunosorbent assay (ELISA).
It was found that there were differences in the distribution of alleles of IL-6 gene polymorphism rs2069830 (p=0.000) and IL-10 gene polymorphism rs3024493 (p=0.007) between the disease group and control group. The frequency of T allele of IL-6 gene polymorphism rs2069830 was higher, while that of IL-10 gene polymorphism rs3024493 was lower in the disease group. Besides, the differences in the distribution of genotypes of IL-6 gene polymorphism rs2069830 (p=0.000) and IL-10 gene polymorphism rs3024493 (p=0.000) were also observed between the disease group and control group. Moreover, the disease group had higher frequencies of TT genotype of IL-6 gene polymorphism rs2069830 and TA genotype of IL-10 gene polymorphism rs3024493. The frequencies of dominant model of IL-6 gene polymorphism rs2069830 (p=0.048) and recessive model of IL-10 gene polymorphism rs3024493 (p=0.000) in the disease group were different from those in the control group. In addition, the frequency of CC + CT dominant model of IL-6 gene polymorphism rs2069830 was lower, and the frequency of TA + AA recessive model of IL-10 gene polymorphism rs3024493 was higher in the disease group. There were differences in haplotypes CG (p=0.001), CT (p=0.007), and TG (p=0.000) of IL-6 gene, as well as haplotypes AA (p=0.002) and AT (p=0.005) of IL-10 gene between disease group and control group. Furthermore, the content of IL-6 in the serum was associated with the genotypes of IL-6 gene polymorphism rs2069830 (p<0.05), whereas the children with acute lymphoblastic leukemia carrying CT genotype had remarkably higher content of serum IL-6. The genotypes of IL-6 gene polymorphism rs2069830 was notably related to white blood cell (WBC) (p=0.002), and the WBC level was higher in children with CT genotype. The genotypes of IL-10 gene polymorphism rs3024489 had prominent correlations with platelet (PLT) (p=0.043), and the children with AA genotype had a higher PLT level. In addition, the genotypes of IL-10 gene polymorphism rs3024493 were evidently correlated with hemoglobin, which was significantly higher in children carrying TA genotype.
The gene polymorphisms of IL-6 and IL-10 are significantly correlated with the susceptibility to and pathogenesis of childhood acute lymphoblastic leukemia.
本研究旨在探讨白细胞介素-6(IL-6)和 IL-10 基因多态性与儿童急性淋巴细胞白血病的相关性。
收集我院 200 例急性淋巴细胞白血病患儿(疾病组)和 200 例正常儿童(对照组)的标本。从两组外周血核细胞中提取 DNA,检测 IL-6 基因 rs2069830 和 rs2069836 以及 IL-10 基因 rs3024489 和 rs3024493 的基因多态性。然后,采用酶联免疫吸附试验(ELISA)法测定血清 IL-6 和 IL-10 含量。
研究发现,疾病组和对照组 IL-6 基因多态性 rs2069830(p=0.000)和 IL-10 基因多态性 rs3024493(p=0.007)的等位基因分布存在差异。IL-6 基因多态性 rs2069830 的 T 等位基因频率较高,而 IL-10 基因多态性 rs3024493 的频率较低。此外,疾病组和对照组 IL-6 基因多态性 rs2069830(p=0.000)和 IL-10 基因多态性 rs3024493(p=0.000)的基因型分布也存在差异。此外,疾病组 IL-6 基因多态性 rs2069830 的 TT 基因型和 IL-10 基因多态性 rs3024493 的 TA 基因型频率较高。IL-6 基因多态性 rs2069830 的显性模型(p=0.048)和 IL-10 基因多态性 rs3024493 的隐性模型(p=0.000)在疾病组中的频率与对照组不同。此外,疾病组 IL-6 基因多态性 rs2069830 的 CC+CT 显性模型频率较低,IL-10 基因多态性 rs3024493 的 TA+AA 隐性模型频率较高。IL-6 基因的 CG(p=0.001)、CT(p=0.007)和 TG(p=0.000)以及 IL-10 基因的 AA(p=0.002)和 AT(p=0.005)单体型在疾病组和对照组之间存在差异。此外,血清中 IL-6 的含量与 IL-6 基因多态性 rs2069830 的基因型有关(p<0.05),而携带 CT 基因型的急性淋巴细胞白血病患儿血清中 IL-6 的含量显著升高。IL-6 基因多态性 rs2069830 的基因型与白细胞(WBC)显著相关(p=0.002),CT 基因型的 WBC 水平较高。IL-10 基因多态性 rs3024489 的基因型与血小板(PLT)显著相关(p=0.043),AA 基因型的 PLT 水平较高。此外,IL-10 基因多态性 rs3024493 的基因型与血红蛋白显著相关,TA 基因型的血红蛋白水平显著升高。
IL-6 和 IL-10 基因多态性与儿童急性淋巴细胞白血病的易感性和发病机制密切相关。