Al-Qahtani A A, Al-Anazi M R, Nazir N, Wani K, Abdo A A, Sanai F M, Khan M Q, Al-Ashgar H I, Albenmousa A, Al-Hamoudi W K, Alswat K A, Al-Ahdal M N
Department of Infection and Immunity, Research Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
Department of Microbiology and Immunology, Alfaisal University School of Medicine, Riyadh, Saudi Arabia.
J Viral Hepat. 2017 Dec;24(12):1132-1142. doi: 10.1111/jvh.12749. Epub 2017 Aug 30.
The aim of this study was to evaluate the association of 10 SNPs in different microRNAs (miRNAs) with susceptibility to hepatitis B virus (HBV) infection, HBV clearance, persistence of chronic HBV infection, and progression to liver cirrhosis and hepatocellular carcinoma (HCC). Patients were categorized into the following groups: inactive HBV carrier, active HBV carrier, HBV-cleared subject and cirrhosis+HCC. Samples were analysed for 10 SNPs in microRNAs using either PCR-based genotyping or the TaqMan assay. We found that rs1358379 was associated with susceptibility to HBV infection, HBV clearance, persistent chronic HBV infection and liver cirrhosis+HCC. In addition, we found that rs2292832 and rs11614913 were associated with risk of HBV infection, viral clearance and cirrhosis+HCC, whereas rs2910164 was associated with proneness to HBV infection, and ability to clear the virus. There was evidence of associations between rs6505162 and HBV clearance and the development of liver disease, whereas a single association was found between rs2289030 and HBV clearance. Similarly, rs7372209 and rs4919510 were specifically associated with the development of HBV-induced liver complications. SNPs in miRNAs affect the susceptibility, clearance and progression of HBV infection in Saudi Arabian patients. We found, using Gene Ontology or pathway analyses, that these genes may contribute to the pathophysiology of HBV infection and related liver complications. However, differences in the association of examined SNPs with various clinical stages indicate variations in the respective functional roles of these polymorphisms and their miRNAs, and thus, further investigation to fully explore their therapeutic potential is warranted.
本研究旨在评估不同微小RNA(miRNA)中的10个单核苷酸多态性(SNP)与乙型肝炎病毒(HBV)感染易感性、HBV清除、慢性HBV感染持续存在以及进展为肝硬化和肝细胞癌(HCC)之间的关联。患者被分为以下几组:非活动性HBV携带者、活动性HBV携带者、HBV清除者以及肝硬化+HCC患者。使用基于聚合酶链反应(PCR)的基因分型或TaqMan检测法对样本中的10个miRNA中的SNP进行分析。我们发现rs1358379与HBV感染易感性、HBV清除、慢性HBV持续感染以及肝硬化+HCC相关。此外,我们发现rs2292832和rs11614913与HBV感染风险、病毒清除以及肝硬化+HCC相关,而rs2910164与HBV感染倾向以及病毒清除能力相关。有证据表明rs6505162与HBV清除以及肝病发展之间存在关联,而rs2289030与HBV清除之间仅发现单一关联。同样,rs7372209和rs4919510与HBV诱导的肝脏并发症的发展具有特异性关联。miRNA中的SNP影响沙特阿拉伯患者HBV感染的易感性、清除以及进展。我们通过基因本体论或通路分析发现,这些基因可能参与HBV感染及相关肝脏并发症的病理生理过程。然而,所检测的SNP与不同临床阶段关联的差异表明这些多态性及其miRNA各自的功能作用存在差异,因此有必要进一步研究以充分探索其治疗潜力。