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标题: 核因子基因多态性及其与肝癌的危险病毒突变的相互作用; [打印本页]

作者: StephenW    时间: 2014-9-24 14:35     标题: 核因子基因多态性及其与肝癌的危险病毒突变的相互作用;

Source: Ann Oncol  |  Posted 14 hours ago
Effect of functional nuclear factor kappaB genetic polymorphisms on hepatitis B virus persistence and their interactions with viral mutations on the risk of hepatocellular carcinoma; Zhang Q, Ji X, Hou X, Lu F, Du Y, Yin J, Sun X, Deng Y, Zhao J, Han X, Yang G, Zhang H, Chen X, Shen H, Wang H, Cao G; Annals of Oncology (Sep 2014)

    Tags:
        Hepatitis
        Liver Cancer


BACKGROUND Non-resolving inflammation and viral mutations are important in hepatitis B virus (HBV)-induced hepatocarcinogenesis. However, the effects of genetic polymorphisms affecting nuclear factor kappaB (NF-κB) on HBV persistence and generation of hepatocellular carcinoma (HCC)-related HBV mutations remain unknown.

PATIENTS AND METHODS rs28362491 (NFKB1 -94Ins>Del), rs2233406 (NFKBIA -826C>T), rs3138053 (NFKBIA -881A>G), and rs696 (NFKBIA +2758G>A) were genotyped in 1,342 healthy controls, 327 HBV-clearance subjects, and 3,976 HBV-positive subjects including 1,495 HCC patients, using quantitative PCR. HBV mutations were determined by sequencing. The NFKBIA promoter activity was assessed by transient transfection. Multiplicative interactions of the polymorphisms and viral mutations were assessed by multivariate logistic regression.

RESULTS Compared to HBV-clearance subjects, rs2233406 (CT versus CC) and rs3138053 (AG or AG+GG versus AA) significantly decreased HBV persistence, especially in the genotype B HBV-infected subjects. In the genotype C HBV-infected subjects, rs2233406 variant genotypes were significantly associated with an increased risk of HCC (CT versus CC: age-, gender-adjusted odds ratio [AOR], 1.33; 95% confidence interval [CI], 1.01-1.75 in training set and AOR, 1.59; 95% CI, 1.01-2.52 in validation set) compared to HCC-free HBV-infected subjects and significantly increased the frequencies of HCC-related HBV mutations (A1762T/G1764A, T1753 V, preS1 start codon mutation, and preS deletion); rs28362491 (Del/Del or Ins/Del+Del/Del versus Ins/Ins) significantly increased the frequency of A1762T/G1764A and reduced the frequency of preS2 start codon mutation. The variant genotypes impaired NFKBIA promoter activity in hepatic cells. The interaction of rs2233406 variant genotypes (CT+TT versue CC) with A1762T/G1764A significantly increased HCC risk in genotype C HBV-infected subjects, with AOR of 2.61 (95% CI, 1.09-6.26).

CONCLUSION Genetic polymorphisms improving NF-κB activity contribute to genotype B HBV clearance. The rs2233406 variant genotypes significantly increase HCC risk, possibly via facilitating immune selection of the HBV mutations. The host-virus interactions are important in identifying HBV-infected subjects who are more likely to develop HCC.

作者: StephenW    时间: 2014-9-24 14:35

来源:安肿瘤学|发布15小时前
效应对乙肝病毒的持久性功能核因子基因多态性及其与肝癌的危险病毒突变的相互作用;张红记,吉X,侯X,吕男,杜Y,阴j,孙X,邓Y,赵Ĵ,韩X,杨G,张辉,陈X,沉H,王华,曹G组;肿瘤科(2014年9月)的纪年

    标签:
        肝炎
        肝癌


背景技术非解决炎症和病毒的突变是在B型肝炎病毒(HBV)诱导的肝癌的重要。然而,对HBV的持久性肝癌的产生影响核因子(NF-κB)的遗传多态性的影响(HCC)相关的HBV突变仍然是未知的。

患者和方法rs28362491(NFKB1-94Ins> DEL),rs2233406(NFKBIA-826C> T),rs3138053(NFKBIA-881A> G)和rs696(NFKBIA+2758G> A)进行基因分型在1342名健康对照,327乙肝病毒清除主题和3,976乙肝病毒阳性者,包括1,495肝癌患者,采用荧光定量PCR。 HBV突变通过测序来确定。该NFKBIA启动子活性通过瞬时转染进行评估。多态性和病毒的突变乘相互作用是由多因素logistic回归评估。

结果相较于乙肝过关科目,rs2233406(CT与CC)和rs3138053(AG或AG + GG与机管局)显著降低乙肝病毒持续存在,特别是在B基因型乙肝病毒感染者。在C基因型乙肝病毒感染者,rs2233406变异基因型显著与肝癌(CT与CC的风险增加有关:年龄,性别调整后胜算比[AOR],1.33;95%信心区间[CI],1.01- 1.75在训练集和AOR,1.59,95%CI,在验证集1.01-2.52)相比,肝癌无乙肝病毒感染者和肝癌相关的HBV突变(A1762T/ G1764A,T1753伏,前S1起始频率显著增加密码子突变和前S缺失); rs28362491(DEL/删除或INS /德尔+ Del键/删除与INS / INS)显著增加A1762T/ G1764A的频率,降低前S2的频率起始密码子突变。变异基因型受损的肝细胞NFKBIA启动子活性。对rs2233406变异基因型(CT+ TT versue CC)与A1762T的互动/ G1764A显著增加2.61(95%CI,1.09-6.26),在C基因型乙肝病毒感染者的HCC危险性,与AOR。

结论遗传多态性提高NF-κB活性有助于B基因型间隙。该rs2233406变异基因型显著增加肝癌的风险,可能通过促进免疫选择的乙肝病毒基因突变。主机 - 病毒相互作用的识别乙肝病毒感染者谁更有可能发展肝癌的重要。
作者: 肝肠欲断    时间: 2014-9-24 21:18


作者: 疯一点好    时间: 2014-9-24 21:53

亚洲人好像都是c基因型多

作者: StephenW    时间: 2014-9-24 22:00

疯一点好 发表于 2014-9-24 21:53
亚洲人好像都是c基因型多

韩国人主要是C,中国北方也是C,但中国南方主要是B.




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