中国西北地区乙型肝炎病毒的基因型，热点突变及其与疾病

StephenW

Biomed Res Int. 2019 Dec 10;2019:3890962. doi: 10.1155/2019/3890962. eCollection 2019.
Genotypes and Hot Spot Mutations of Hepatitis B Virus in Northwest Chinese Population and Its Correlation with Diseases Progression.
Wang W#1,2,3, Shu Y#1,2, Bao H1,2, Zhao W1,2, Wang W1,2, Wang Q1,2, Lei X1,2, Cui D4, Yan Z1,2.
Author information

1
    The State Key Laboratory of Cancer Biology, Air Force Military Medical University, Xi'an 710032, China.
2
    Department of Biopharmaceutics, School of Pharmacy, Air Force Medical University, Xi'an 710032, China.
3
    Department of Pharmaceutics and Pharmacy Administration, School of Pharmacy, Air Force Medical University, Xi'an 710032, China.
4
    Department of Bio-Nano Science and Engineering, Key Laboratory for Thin Film and Microfabrication of Ministry of Education, Institute of Micro-Nano Science and Technology, Shanghai Jiao Tong University, Shanghai 200240, China.
#
    Contributed equally

Abstract

Hepatitis B virus (HBV) infection is a critical incentive for chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Different genotypes and genome mutations of HBV have been found to be related to the progression of these liver diseases. However, their clinical significance is still under debate. The objective of this study was to determine the association of HBV genotypes and hot spot mutations in the reverse transcriptase (RT) and basal core promoter-precore (BCP-PreC) region with HBV-infected diseases in a northwest Chinese population. HBV genotyping and DNA sequencing were performed in samples of 980 patients. Appropriate statistical methods were adopted to assess HBV genetic features and its clinical association. It was found that the prevalent HBV genotype in northwestern Chinese patients was HBV/C (61.33%), followed by HBV/B (36.63%). In RT region, in addition to the reported nucleoside analogue- (NA-) resistance missense mutations, new silent mutations at rt169 and rt180 were found to raise the risk of HCC in patients with HBV/C. And the heterozygous mutation status of rt169/rt180 was associated with the increased risk of both HCC and NA resistance (OR > 1, P < 0.01) regardless of HBV genotypes. In BCP-PreC region, multiple mutations and combinations, especially at nt 1762/1764 and nt 1896/1899, were characterized to be the causes of spurious HBeAg negativity and liver function injury, as well as the risk factors for HCC progression (P < 0.01). Additionally, a novel mutation at nt1799G>C was likely found to increase the risk of HCC in patients with HBV/B. These findings revealed an association between HBV genotypes and HBV genetic mutations in RT and BCP-PreC region and progression of hepatitis B. It would be helpful for risk evaluation and diagnostic improvement based on these genetic features.

Copyright © 2019 Wei Wang et al.

PMID:
    31886206
PMCID:
    PMC6925797
DOI:
    10.1155/2019/3890962

StephenW

Biomed Res Int。 2019年12月10日; 2019：3890962. Doi：10.1155 / 2019/3890962。 ECollection 2019。
中国西北地区乙型肝炎病毒的基因型，热点突变及其与疾病进展的相关性。
Wang W＃1,2,3，Shu Y＃1,2，Bao H1,2，Zhao W1,2，Wang W1,2，Wang Q1,2，Lei X1,2，Cui D4，Yan Z1,2。
作者信息

1个
空军军医大学肿瘤生物学国家重点实验室，西安710032
2
空军医科大学药学院生物制药系，西安710032
3
空军医科大学药学院药剂与药政管理系，西安710032
4
上海交通大学生物纳米科学与工程系，薄膜与微细加工教育部重点实验室，上海交通大学微纳米科学技术研究所，上海200240
＃
平均贡献

抽象

乙型肝炎病毒（HBV）感染是慢性乙型肝炎（CHB），肝硬化（LC）和肝细胞癌（HCC）的重要诱因。已经发现HBV的不同基因型和基因组突变与这些肝病的进展有关。但是，它们的临床意义仍在争论中。这项研究的目的是确定在中国西北地区，HBV基因型和逆转录酶（RT）和基础核心启动子前核心（BCP-PreC）地区热点突变与HBV感染疾病的关系。在980例患者的样本中进行了HBV基因分型和DNA测序。采用适当的统计方法评估HBV的遗传特征及其临床关联性。结果发现，在中国西北地区患者中流行的HBV基因型为HBV / C（61.33％），其次是HBV / B（36.63％）。在RT区，除了已报道的核苷类似物（NA-）抗性错义突变外，在rt169和rt180处发现新的沉默突变会增加HBV / C患者的HCC风险。并且rt169的杂合突变状态/ rt180与HBV基因型无关的HCC和NA耐药风险增加（OR> 1，P <0.01）。在BCP-PreC区，多种突变和组合，尤其是在1762/1764 nt和1896/1899 nt突变，被认为是伪造HBeAg阴性和肝功能损伤的原因，以及HCC进展的危险因素（P < 0.01）。此外，可能发现nt1799G> C处的新突变会增加HBV / B患者的HCC风险。这些发现揭示了RT和BCP-PreC区HBV基因型与HBV基因突变与乙型肝炎的进展之间存在关联。基于这些遗传特征，将有助于风险评估和诊断改善。

版权所有©2019 Wei Wang等。

PMID：
31886206
PMCID：
PMC6925797
DOI：
10.1155 / 2019/3890962

StephenW

http://downloads.hindawi.com/journals/bmri/2019/3890962.pdf