HLA-DQB1等位基因多态性及Th1/Th2细胞相关因子与广西瑶族肝癌家族聚集性的相关性

Relationship between HLA-DQB1 allele as well as expression level of Th1/Th2 cytokines with familial clustering of hepatocellular carcinoma in Guangxi yao

目的:探讨HLA-DQB1等位基因多态性及相应位点下Th1/Th2细胞相关因子IL-2、IL-4及IL-10对广西瑶族原发性肝癌家族聚集性的影响,为寻找广西瑶族原发性肝癌的遗传易感基因或拮抗基因提供线索。方法:在广西肝癌高发区选取民族为瑶族的肝癌高发家族成员、无癌家族成员各40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,应用PCR-SSP的方法对HLA-DQB1等位基因进行检测,应用ELISA法检测IL-2、IL-4、IL-10的水平。结果:(1)广西瑶族肝癌高发家族组的HLA-DQB1*02/09等位基因表达频率高于无癌家族组,两组比较差异明显,具有统计学意义(P<0.05);而两组间的HLA-DQB1*04/05/06/07/08等位基因表达频率无显著性差异(P>0.05)。(2)HLADQB1各等位基因在乙型肝炎病毒感染组(HBs Ag阳性组)及非乙型肝炎病毒感染组(HBs Ag阴性组)间的分布频率比较无显著性差异(P值均>0.05)。(3)广西瑶族肝癌高发家族成员组中Th2细胞相关因子IL-4、IL-10平均表达水平高于无癌家族成员组,差异具有统计学意义(P<0.05),而两组间的IL-2浓度无显著性差异(P>0.05)。(4)两组中HLA-DQB1*02阳性成员的IL-10平均表达水平高于HLA-DQB1*02阴性成员,差异具有统计学意义(P<0.05)。(5)两组中HLA-DQB1*09阳性成员的IL-4平均表达水平高于HLA-DQB1*09阴性成员,差异具有统计学意义(P<0.05)。结论:(1)HLA-DQB1*02/09等位基因可能是广西瑶族居民原发性肝癌发生的易感基因。(2)HLA-DQB1各等位基因与广西瑶族居民的HBV感染可能无显著相关性。(3)IL-4、IL-10表达水平失衡可能是广西瑶族肝癌家族聚集性的危险因素。(4)IL-10表达水平失衡可能与HLADQB1*02等位基因的携带有关,而IL-4表达水平失衡可能与HLA-DQB1*09等位基因的携带有关,它们之间共同作用可能与广西瑶族肝癌家族聚集性的发生有相关性。

Objective：To elucidate the relationship between HLA-DQB1 allele polymorphism as well as the expression level of Th1/Th2 cytokines with familial clustering of hepatocellular carcinoma（HCC） to provide some evidence for the seeking susceptibility gene or resistant gene of HCC in Guangxi yao,China.Methods：With the same sexuality,age ± 5 year,40 members whose families have had two or more HCC patients（high-occurrence families） were selected as the case group,and 40 members whose families have no any cancer patient were selected as the controls.Peripheral blood samples were collected to extract DNA,PCR-SSP was used to detect HLADQB1 alleles and ELISA was used to detect IL-2,IL-4 and IL-10.Results：（1） The gene frequency of the HLA-DQB1＊ 02/09 alleles in the case group was higher than that in the controls（P〈0.05）;but the gene frequency of the HLA-DQB1＊ 04/05/06/07/08 alleles were never significant difference between two groups（P〉0.05）.（2） The gene frequency of alleles HLA-DQB1 in HBs Ag positive group and HBs Ag negative group were never significant difference（P〉0.05）.（3） The expression levels of IL-4,IL-10 in the case group was higher than that in the control（P〈0.05）.（4） The expression level of IL-10 in the positive group of the HLA-DQB1＊ 02 allele was higher than that in the negative group of the HLA-DQB1＊ 02 allele（P〈0.05）.（5） The expression level of IL-4 in the positive group of the HLA-DQB1＊ 09 allele was higher than that in the negative group of the HLA-DQB1＊ 09 allele（P〈0.05）.Conclusion：（1） HLA-DQB1＊ 02/09 seem to be susceptibility genes of hepatocellular carcinoma in high HCC incidence areas of Guangxi yao.（2）There may be not significant correlation bewteen HLA-DQB1 alleles and the susceptibility of HBV infection in high HCC incidence are-as of Guangxi yao.（3） The imbalance of IL-4,IL-10 might be associated with familial clustering of hepatocellular carcinoma in Guangxi yao.（4） The imbalance of IL-10 might be due to the carrying of HLA-DQB1＊ 02;the imbalance of IL-4 might be due to the carrying of HLA-DQB1＊ 09.Through the same approaches,these might lead to the phenomenon of familial aggregation of HCC in Guangxiyao.