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摘要：
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摘要：目的 探讨信号转导与转录激活因子4（signal transducer and activator of transcription 4，STAT4）
rs7574865基因多态性与HBV感染相关肝细胞癌（hepatocellular carcinoma，HCC）的相关性。方法 选取
2017年1月至2018年1月于宜兴市人民医院确诊的142例HBV感染相关HCC患者和100例健康体检者为研究
对象。根据是否有乙型肝炎家族史将HBV感染相关HCC患者分为乙型肝炎家族史组（82例）和无乙型
肝炎家史组（60例）。根据HBV DNA检测下限，将HBV感染相关HCC患者分为HBV DNA高于检测下
限组（HBV DNA ≥ 10 3 IU/ml，64例）和HBV DNA低于检测下限组（HBV DNA ＜ 10 3 IU/ml，78例）；
根据HBV DNA病毒载量，将HBV DNA高于检测下限组分为高病毒载量组（HBV DNA ≥ 10 4 IU/ml，30
例）和低病毒载量组（10 3 IU/ml ＜ HBV DNA ＜ 10 4 IU/ml，34例）。采用Taq Man MGB实时荧光定量
PCR技术检测STAT4 rs7574865基因多态性。分别比较不同组间STAT4 rs7574865基因型分布。结果 HBV
感染相关HCC组患者STAT4 rs7574865 G等位基因频率显著高于健康对照组（χ 2 = 28.831，P ＜ 0.001）；
有乙型肝炎家族史组STAT4 rs7574865 G等位基因频率显著高于无乙型肝炎家族史组（χ 2 = 17.458，P ＜
0.001）；HBV DNA高于检测下限组STAT4 rs7574865 G等位基因频率显著高于HBV DNA低于检测下限组
（χ 2 = 10.178，P = 0.001）；高病毒载量组STAT4 rs7574865 G等位基因频率显著高于低病毒载量组（χ 2 =
16.875，P ＜ 0.001）。HBV相关HCC患者中，STAT4 rs7574865基因GG、GT和TT基因型患者AFP水平差
异有统计学意义（F = 6.128，P = 0.003），GG基因型患者AFP水平显著高于TT基因型患者（t = 8.341，
P = 0.002）。结论 STAT4 rs7574865可能是HBV相关HCC及家族性HBV相关HCC的易感基因；STAT4
rs7574865 G等位基因可能参与HBV DNA复制并与高病毒载量有关。STAT4 rs7574865基因多态性可能会
影响HBV感染相关HCC患者血清AFP水平。
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Abstract: Objective To investigate the correlation between polymorphisms of STAT4 rs7574865 and
hepatitis B virus (HBV) infection related hepatocellular carcinoma (HCC). Methods Total of 142 patients
with HBV infection related HCC and 100 healthy controls in People’s Hospital of Yixing from January 2017
to January 2018 were selected. According to whether there with family history of hepatitis B, patients with
HBV infection related HCC were divided into with family history of hepatitis B group (82 cases) and without
family history of hepatitis B group (60 cases). According to the lower limit of HBV DNA detection, patients
with HBV infection related HCC were divided into HBV DNA higher than the lower limit group (HBV
DNA ≥ 10 3 IU/ml, 64 cases) and HBV DNA lower than the lower limit group (HBV DNA ＜ 10 3 IU/ml,
78 cases); and according to the viral load of HBV DNA, patients in HBV DNA higher than the lower limit
group were divided into high viral load group (HBV DNA ≥ 10 4 IU/ml, 30 cases) and low viral load group
(10 3 IU/ml ＜ HBV DNA ＜ 10 4 IU /ml, 34 cases). The STAT4 rs7574865 gene polymorphism was detected
by Taq Man MGB real-time PCR. The distribution of STAT4 rs7574865 genotypes in different groups were
compared. Results The STAT4 rs7574865 G allele frequency of patients in HBV infection related HCC
group was significantly higher than that in healthy controls (χ 2 = 28.831, P ＜ 0.001). The STAT4 rs7574865
G allele frequency of patients with family history of hepatitis B was significantly higher than that without
family history of hepatitis B (χ 2 = 17.458, P ＜ 0.001). The STAT4 rs7574865 G allele frequency of patients
in HBV DNA higher than the lower limit group was significantly higher than that in HBV DNA lower than
the lower limit group (χ 2 = 10.178, P = 0.001). The STAT4 rs7574865 G allele frequency of patients in high
viral load group was significantly higher than that in low viral load group (χ 2 = 16.875, P ＜ 0.001). Among
HBV-infection related HCC patients, the AFP levels of GG, GT and TT genotypes of STAT4 rs7574865
were significantly different (F = 6.128, P = 0.003). The AFP levels of patients with GG genotype were
significantly higher than those with TT genotype (t = 8.341, P = 0.002). Conclusions STAT4 rs7574865 may
be a susceptibility and familial gene for HBV infection related HCC. The STAT4 rs7574865 G allele may
be involved in HBV DNA replication and is associated with high viral load. The STAT4 rs7574865 gene
polymorphism may affect serum AFP levels in patients with HBV infection related HCC.
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