与自噬相关的5基因rs510432多态性与慢性乙型肝炎病毒感染患

StephenW

Immunol Invest. 2019 Mar 25:1-14. doi: 10.1080/08820139.2019.1567532. [Epub ahead of print]
Autophagy-Related 5 Gene rs510432 Polymorphism Is Associated with Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Virus Infection.
Li N1, Fan X1, Wang X1, Deng H1, Zhang K1, Zhang X1, Han Q1, Lv Y2,3, Liu Z1,3.
Author information

1
    a Department of Infectious Diseases , First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi , People's Republic of China.
2
    b Department of Hepatobiliary Surgery , First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi , People's Republic of China.
3
    c Institute of Advanced Surgical Technology and Engineering , Xi'an Jiaotong University , Xi'an , Shaanxi , People's Republic of China.

Abstract
BACKGROUND:

Despite the identification of autophagy-related protein 5 (ATG5) as a molecule involved in the activated autophagy machinery during hepatitis B virus (HBV) infection and hepatocarcinogenesis, the consequences of ATG5 mutation carriage for patients with chronic HBV infection remain unclear. This study examined the association of ATG5 polymorphisms with HBV-related diseases including hepatocellular carcinoma (HCC).
PATIENTS AND METHODS:

Two functionally relevant polymorphisms ATG5 rs573775 and rs510432 were genotyped by ligase detection reaction-polymerase chain reaction in 403 patients with chronic HBV infection (171 chronic hepatitis, 119 cirrhosis and 113 HCC) and 196 healthy controls. Univariate and multivariate logistic regression was performed to evaluate factors associated with HCC.
RESULTS:

The rs573775 genotype and allele frequencies had no significant differences between patients with different clinical diseases. However, HCC patients had significantly higher frequency of rs510432 genotype AA (odds ratio [OR] 2.185, 95% confidence interval [CI] 1.042-4.581, P = 0.037, P value by Bonferroni correction [Pc] = 0.074) and allele A (OR 1.435, 95% CI 1.023-2.013, Pc = 0.036) than chronic hepatitis patients. In multivariate analyses, rs510432 allele A-containing genotypes (AA+GA) were independently associated with cirrhosis in comparison to chronic hepatitis (OR 1.927, 95%CI 1.011-3.017, P = 0.032). The rs510432 genotypes AA+GA were also independently associated with HCC in comparison to chronic hepatitis (OR 2.583, 95% CI 1.025-3.911, P = 0.006) or chronic HBV infection without HCC (OR 2.632, 95% CI 1.067-3.482, P = 0.032).
CONCLUSION:

These results indicate that rs510432 genotypes AA+GA are associated with disease progression and HCC risk in chronic HBV infection, providing novel evidence for a role of ATG5 in the pathogenesis of HBV-related HCC.
ABBREVIATIONS:

HBV: hepatitis B virus; HCC hepatocellular carcinoma; TNFSF10: tumor necrosis factor superfamily member 10; ATG5: autophagy-related protein 5; DNA: deoxyribonucleic acid; LDR-PCR: ligase detection reactions-polymerase chain reaction; PCR: polymerase chain reaction; SLE: systemic lupus erythematosus; BD: Behçet's disease; IL-10: interlukin-10; LPS: lipopolysaccharide; PBMC: peripheral blood mononuclear cells; CWP: coal workers' pneumoconiosis; TNF-α: tumor necrosis factor-α.
KEYWORDS:

ATG5; Hepatitis B virus infection; hepatocellular carcinoma; polymorphism

PMID:
    30907204
DOI:
    10.1080/08820139.2019.1567532

StephenW

Immunol投资。 2019年3月25日：1-14。 doi：10.1080 / 08820139.2019.1567532。 [印刷前的电子版]
与自噬相关的5基因rs510432多态性与慢性乙型肝炎病毒感染患者的肝细胞癌相关。
Li N1，Fan X1，Wang X1，Deng H1，Zhang K1，Zhang X1，Han Q1，Lv Y2,3，Liu Z1,3。
作者信息

1
西安交通大学第一附属医院传染病科，陕西西安，中华人民共和国。
2
b西安交通大学第一附属医院肝胆外科，陕西西安，中华人民共和国。
3
c西安交通大学高级外科技术与工程研究所，陕西西安，中华人民共和国。

抽象
背景：

尽管在乙型肝炎病毒（HBV）感染和肝癌发生过程中鉴定了自噬相关蛋白5（ATG5）作为参与激活的自噬机制的分子，但ATG5突变携带对慢性HBV感染患者的影响仍不清楚。 ATG5多态性与HBV相关疾病（包括肝细胞癌（HCC））的关联。
患者和方法：

两个功能相关的多态性ATG5 rs573775和rs510432通过连接酶检测反应 - 聚合酶链反应对403例慢性HBV感染患者（171例慢性肝炎，119例肝硬化和113例HCC）和196例健康对照进行基因分型。进行单变量和多变量逻辑回归以评估与HCC相关的因素。
结果：

rs573775基因型和等位基因频率在不同临床疾病患者之间无显着差异。然而，HCC患者rs510432基因型AA的频率显着较高（优势比[OR] 2.185,95％置信区间[CI] 1.042-4.581，P = 0.037，Bonferroni校正P值[Pc] = 0.074）和等位基因A（ OR 1.435,95％CI 1.023-2.013，Pc = 0.036）比慢性肝炎患者。在多变量分析中，rs510432等位基因A含有基因型（AA + GA rs510432基因型AA + GA与慢性肝炎（OR 2.583,95％）CI 1.025-3.911，P = 0.006）或慢性HBV相比也与HCC独立相关没有HCC的感染（OR 2.632,95％CI 1.067-3.482，P = 0.032）。
结论：

这些结果表明rs510432基因型AA + GA与慢性HBV感染的疾病进展和HCC风险相关，为ATG5在HBV相关HCC的发病机制中的作用提供了新的证据。
缩写：

HBV：乙型肝炎病毒; HCC肝细胞癌; TNFSF10：肿瘤坏死因子超家族成员10; ATG5：自噬相关蛋白5; DNA：脱氧核糖核酸; LDR-PCR：连接酶检测反应 - 聚合酶链反应; PCR：聚合酶链反应; SLE：系统性红斑狼疮; BD：Behçet病; IL-10：白细胞介素-10; LPS：脂多糖; PBMC：外周血单核细胞; CWP：煤炭工人的尘肺病; TNF-α：肿瘤坏死因子-α。
关键词：

ATG5;乙型肝炎病毒感染;肝细胞癌;多态性

结论：
30907204
DOI：
10.1080 / 08820139.2019.1567532