Correlations of IL-18 and IL-6 gene polymorphisms and expression levels with onset of glioma

Y. Yang, Y.-J. Song, Q.-B. Nie, Y.-F. Wang, M. Zhang, G.-S. Mao

Department of Neurosurgery, The Third Medical Center, Chinese PLA (People’s Liberation Army) General Hospital, Beijing, China. yzb@ahmu.edu.cn

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• Genetics
• Oncology

OBJECTIVE:  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.

PATIENTS AND METHODS: 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.

RESULTS: 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).

CONCLUSIONS: IL-18 and IL-6 gene polymorphisms and expression levels are significantly correlated with the onset of glioma.

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