Department of Neurosurgery, The Third Medical Center, Chinese PLA (People's Liberation Army) General Hospital, Beijing, China.
Eur Rev Med Pharmacol Sci. 2022 Mar;26(5):1475-1483. doi: 10.26355/eurrev_202203_28211.
The aim of this study was to explore the correlations of interleukin (IL)-18 and IL-6 gene polymorphisms and expression levels with the onset of glioma.
The differences in the expression levels of IL-18 and IL-6 between glioma patients and normal people in the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases were analyzed. A total of 200 glioma patients and 200 healthy people were taken as the research subjects. Peripheral blood was collected to extract deoxyribonucleic acids (DNAs). IL-18 and IL-6 gene polymorphisms were detected and analyzed combined with haplotype analysis and gene expression levels of IL-18 and IL-6, as well as their levels in serum.
Both IL-18 and IL-6 were highly expressed in tumor tissues of glioma patients, whereas they were lowly expressed in normal cerebral tissues, with statistically significant differences (p<0.05). Statistically significant differences in the allele distributions of IL-18 gene polymorphisms rs371411440 (p=0.041) and rs371828055 (p=0.002) and IL-6 gene polymorphisms rs201211345 (p=0.000) and rs201439472 (p=0.003) were observed between disease group and control group (p<0.05). Genotype distributions of IL-18 gene polymorphism rs371828055 (p=0.005) and IL-6 gene polymorphisms rs201211345 (p=0.000) and rs201439472 (p=0.019) in disease group were significantly different from those in control group (p<0.05). Disease group exhibited significantly higher frequencies of genotype GG of IL-18 gene polymorphism rs371828055, genotype AA of IL-6 gene polymorphism rs201211345 and genotype TT of IL-6 gene polymorphism rs201439472 than control group (p<0.05). There were statistically significant differences in the distributions of the dominant model AA+AC of IL-6 gene polymorphism rs201211345 (p=0.016) and the recessive model GT+TT of IL-18 gene polymorphism rs371828055 (p=0.010) between the two groups (p<0.05). Differences in the distributions of haplotypes CC (p=0.001) and GT (p=0.027) of IL-18 gene polymorphisms rs371411440 and rs371828055 and haplotypes AC (p=0.009), AT (p=0.000) and CT (p=0.000) of IL-6 gene polymorphisms rs201211345 and rs201439472 were observed between disease group and control group (p<0.05). In addition, a high degree of linkage disequilibrium was detected between IL-6 gene polymorphisms rs201211345 and rs201439472 (D'=0.583). The genotypes of IL-18 gene polymorphism rs371828055 were evidently correlated with the gene expression of IL-18 (p=0.000). Meanwhile, patients with genotype GT had a distinctly lower expression level of IL-18 (p<0.05). The genotypes of IL-6 gene polymorphism rs201211345 were obviously associated with the expression of IL-6 (p=0.002). The expression of IL-6 was markedly down-regulated in patients carrying genotype AA (p<0.05). Consistent with the expression levels of IL-18 and IL-6, the genotypes of IL-18 gene polymorphism rs371828055 were associated with the content of serum IL-18 (p<0.05). Moreover, patients carrying genotype GT had distinctly lower content of serum IL-18 (p<0.05). Additionally, the genotypes of IL-6 gene polymorphism rs201211345 were evidently correlated with the content of serum IL-6 (p<0.05), and the content of serum IL-6 declined distinctly in patients with genotype AA (p<0.05).
IL-18 and IL-6 gene polymorphisms and expression levels are significantly correlated with the onset of glioma.
本研究旨在探讨白细胞介素（IL）-18 和 IL-6 基因多态性及其表达水平与脑胶质瘤发病的相关性。
分析癌症基因组图谱（TCGA）和组织表达（GTEx）数据库中脑胶质瘤患者与正常人之间的 IL-18 和 IL-6 基因表达水平的差异。选取 200 例脑胶质瘤患者和 200 名健康人作为研究对象。采集外周血提取脱氧核糖核酸（DNA）。结合单倍型分析和 IL-18 和 IL-6 基因表达水平及其血清含量，检测并分析 IL-18 和 IL-6 基因多态性。
脑胶质瘤患者肿瘤组织中 IL-18 和 IL-6 均呈高表达，而正常脑组织中 IL-18 和 IL-6 呈低表达，差异均有统计学意义（p<0.05）。IL-18 基因 rs371411440（p=0.041）和 rs371828055（p=0.002）、IL-6 基因 rs201211345（p=0.000）和 rs201439472（p=0.003）等位基因分布在疾病组和对照组之间差异均有统计学意义（p<0.05）。IL-18 基因 rs371828055 （p=0.005）和 IL-6 基因 rs201211345（p=0.000）、rs201439472（p=0.019）的基因型分布在疾病组与对照组之间差异有统计学意义（p<0.05）。疾病组 IL-18 基因 rs371828055 基因型 GG、IL-6 基因 rs201211345 基因型 AA 和 rs201439472 基因型 TT 的频率明显高于对照组（p<0.05）。IL-6 基因 rs201211345 显性模型 AA+AC（p=0.016）和 IL-18 基因 rs371828055 隐性模型 GT+TT（p=0.010）的分布在两组间差异均有统计学意义（p<0.05）。IL-18 基因 rs371411440 和 rs371828055 的单倍型 CC（p=0.001）和 GT（p=0.027）、IL-6 基因 rs201211345 和 rs201439472 的单倍型 AC（p=0.009）、AT（p=0.000）和 CT（p=0.000）在疾病组和对照组之间差异均有统计学意义（p<0.05）。此外，IL-6 基因 rs201211345 和 rs201439472 之间存在高度连锁不平衡（D'=0.583）。IL-18 基因 rs371828055 基因型与 IL-18 基因表达明显相关（p=0.000）。同时，GT 基因型患者的 IL-18 表达水平明显较低（p<0.05）。IL-6 基因 rs201211345 基因型与 IL-6 表达明显相关（p=0.002）。携带 AA 基因型的患者的 IL-6 表达明显下调（p<0.05）。与 IL-18 和 IL-6 的表达水平一致，IL-18 基因 rs371828055 基因型与血清 IL-18 含量相关（p<0.05）。携带 GT 基因型的患者血清 IL-18 含量明显较低（p<0.05）。此外，IL-6 基因 rs201211345 基因型与血清 IL-6 含量明显相关（p<0.05），携带 AA 基因型的患者血清 IL-6 含量明显下降（p<0.05）。
IL-18 和 IL-6 基因多态性及其表达水平与脑胶质瘤的发病明显相关。
