Department of Laboratory Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
302 Hospital of PLA, Beijing, China.
Infect Genet Evol. 2021 Jan;87:104638. doi: 10.1016/j.meegid.2020.104638. Epub 2020 Nov 21.
Inflammatory cytokine gene polymorphisms may influence the hepatic and extrahepatic HBV-related disease. In this study, we aimed to investigate the relationship between polymorphisms of IL-17, IL-21 gene and HBV related hepatocellular carcinoma in Chinese Han population.
We performed a multi-center study comprised 866 HBV-related hepatocellular carcinoma (HCC) patients and 1086 unrelated patients with a diagnosis of chronic hepatitis B (CHB) as control to evaluate the effects of IL-17 (rs4711998), IL-21 SNPs (rs12508721, rs13143866 and rs2221903) and the susceptibility of HCC. MassARRAY technology was utilized to genotype. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum IL-17 and IL-21 level. Quantitative real time polymerase chain reaction (qRT-PCR) was used to analyze the serum viral loads.
In logistic regression analysis, our results showed the frequency of rs4711998 allele G in CHB group was significantly higher than that in HCC group (P = 0.042, 0.859(0.743-0.994)), and it is present only among females. Compared to HCC group, rs13143866 A allele was more likely to appear in HCC group (P = 0.015, 1.268 (1.049-1.532)). The frequency of AA also showed different between HCC group and CHB groups (P = 0.011, 3.135 (1.292-7.603)), which showed strong sex-specific relationships. ELISA showed a higher serum IL-17 and IL-21 expression in HCC patients compared to CHB patients (P all <0.05). Haplotype rs12508721C/rs13143866A/rs2221903T in male HCC group was statistically higher than in male CHB group(P = 0.013) but not in females (P > 0.05).
We suggested rs4711998 allele A as risk factors for women to develop HBV related-HCC in Chinese Han population. rs13143866 allele A as risk factors to develop HBV related-HCC in Chinese male population. Male patients with haplotype rs12508721C/rs13143866A/rs2221903T may with 1.3-fold risk for HBV-related HCC.
炎症细胞因子基因多态性可能影响与乙型肝炎病毒相关的肝内外疾病。本研究旨在探讨白细胞介素-17（IL-17）和白细胞介素-21（IL-21）基因多态性与中国汉族人群乙型肝炎病毒相关性肝细胞癌（HCC）的关系。
我们进行了一项多中心研究，包括 866 例乙型肝炎病毒相关性肝细胞癌（HCC）患者和 1086 例慢性乙型肝炎（CHB）患者作为对照，以评估 IL-17（rs4711998）、IL-21 SNPs（rs12508721、rs13143866 和 rs2221903）的多态性与 HCC 的易感性。采用 MassARRAY 技术进行基因分型。酶联免疫吸附试验（ELISA）检测血清 IL-17 和 IL-21 水平。实时荧光定量聚合酶链反应（qRT-PCR）分析血清病毒载量。
在逻辑回归分析中，我们的结果显示 CHB 组 rs4711998 等位基因 G 的频率明显高于 HCC 组（P=0.042，0.859（0.743-0.994）），且仅存在于女性中。与 HCC 组相比，rs13143866A 等位基因在 HCC 组中更为常见（P=0.015，1.268（1.049-1.532））。AA 频率在 HCC 组和 CHB 组之间也存在差异（P=0.011，3.135（1.292-7.603）），这表明存在明显的性别特异性关系。ELISA 显示 HCC 患者血清 IL-17 和 IL-21 表达高于 CHB 患者（均 P<0.05）。在男性 HCC 组中，rs12508721C/rs13143866A/rs2221903T 单体型明显高于男性 CHB 组（P=0.013），但在女性中无统计学差异（P>0.05）。
我们认为 rs4711998 等位基因 A 是中国汉族女性发生乙型肝炎病毒相关 HCC 的危险因素。rs13143866 等位基因 A 是中国男性发生乙型肝炎病毒相关 HCC 的危险因素。男性患者携带 rs12508721C/rs13143866A/rs2221903T 单体型可能使乙型肝炎病毒相关 HCC 的风险增加 1.3 倍。
