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本研究探讨HLA-DQB1~*02、03等位基因及细胞因子IFN-γ和IL-4与广西壮、瑶族肝癌家庭聚集性的相关性。将来自肝癌高发区,民族为瑶族的肝癌高发家族成员、无癌家族成员各40例及民族为壮族的肝癌高发家族成员、无癌家族成员各48例作为研究对象(采用相同性别,年龄(±5岁)配对方法),采集研究对象外周血并提取全血DNA,采用PCR-SSP技术检测受试者的HLA-DQB1~*02和HLA-DQB1~*03等位基因,IFN-γ及IL-4细胞因子表达水平采用ELISA法检测。结果发现,HLA-DQB1~*02、03基因在壮族肝癌高发家族成员组的表达频率均低于无癌家族成员组(p<0.05);HLA-DQB1~*02基因在瑶族肝癌高发家族成员组的表达频率高于无癌家族组(p=0.002),HLA-DQB1~*03在两组间的表达频率无明显差异(p>0.05)。广西壮、瑶族人群HLA-DQB1~*02、03基因在乙肝病毒感染组及非感染组中的表达频率比较无显著性差异(p>0.05)。壮、瑶族肝癌高发家族成员组IL-4平均表达水平均高于无癌家族成员组,肝癌高发家族成员组IFN-γ平均表达水平均低于无癌家族成员组,差异具有统计学意义(p<0.05)。广西壮、瑶族人群中HLA-DQB1~*02基因阳性和阴性成员的IL-4平均表达水平无明显差异(p>0.05)。广西壮族人群中HLA-DQB1~*03基因阳性成员的IFN-γ平均表达水平高于HLA-DQB1~*03阴性成员(p=0.011),HLA-DQB1~*03阳性和阴性成员的IL-4平均表达水平无明显差异(p<0.05)。本课题得出结论,HLA-DQB1~*02、03基因与广西壮、瑶族肝癌家庭聚集性有关,但存在较大的民族差异;细胞因子IFN-γ及IL-4的表达水平失衡可能是广西壮、瑶族肝癌家族聚集性的危险因素。HLA-DQB1~*03基因导致广西壮族肝癌家族聚集性的发生可能是通过影响IFN-γ的表达水平来实现的。
This study was to investigate the association of HLA-DQB1 * 02,03 alleles and cytokines IFN-γ and IL-4 with familial aggregation of hepatocellular carcinoma in Zhuang and Yao in Guangxi. Forty-four HCC patients with high prevalence of HCC, ethnic HCC patients, 40 cancer-free HCCs and 48 HCC patients without HCC were enrolled as study subjects (using the same sex, age (± 5-year-old paired). The peripheral blood was collected and the whole blood DNA was extracted. The alleles of HLA-DQB1 ~ * 02 and HLA-DQB1 ~ * 03 were detected by PCR-SSP. IFN- -4 cytokine expression levels by ELISA assay. The results showed that the frequencies of HLA-DQB1 ~ * 02,03 genes were significantly lower than those of non-cancer family members (P <0.05), and the frequencies of HLA-DQB1 * (P = 0.002). There was no significant difference in the expression frequency of HLA-DQB1 ~ * 03 between the two groups (p> 0.05). The frequencies of HLA-DQB1 * 02,03 genes in the Zhuang and Yao ethnic groups in Guangxi were not significantly different from those in the non-infected and non-infected groups (p> 0.05). The average expression of IL-4 in the family members with high prevalence of hepatocellular carcinoma in Zhuang and Yao was higher than that in the non-cancer family members and the average expression of IFN-γ in the members with high incidence of HCC was lower than that in the non-cancer family members (p <0.05). There was no significant difference in the mean IL-4 expression level between HLA-DQB1 * * 02 gene positive and negative in Zhuang and Yao ethnic groups in Guangxi (p> 0.05). The mean IFN-γ expression level of HLA-DQB1 * * 03 positive members in Guangxi Zhuang population was higher than that of HLA-DQB1 * * 03 negative members (p = 0.011), HLA-DQB1 ~ * 03 positive and negative members The average expression level had no significant difference (p <0.05). This topic concludes that HLA-DQB1 ~ * 02,03 gene is associated with familial aggregation of hepatocellular carcinoma in Zhuang and Yao ethnic groups in Guangxi, but there is a big ethnic difference. The imbalance of cytokine IFN-γ and IL-4 may be Guangxi Zhuang, Yao family members of liver cancer risk factors. The HLA-DQB1 ~ * 03 gene led to the occurrence of family aggregation of hepatocellular carcinoma in Guangxi Zhuang Autonomous Region possibly by affecting the expression of IFN-γ.