Pharmacy Department, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.
Department of Clinical Laboratory, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
J Clin Lab Anal. 2022 Jul;36(7):e24530. doi: 10.1002/jcla.24530. Epub 2022 Jun 3.
It was known that mutations in the RT region were mainly related to nucleot(s)ide analogs resistance. Increasing studies indicated that RT mutations were related to advanced liver diseases (ALD) and had effects on HBV replication, but the distribution characteristics of mutations across RT region in the development of liver diseases and the effect of RT mutations on HBV replication were not fully clarified. HBV RT region was direct-sequenced in 1473 chronic HBV-infected patients. Mutation frequencies were analyzed to identify the specific mutations differing between groups classified by genotypes, loads of HBV DNA, or progression of liver diseases. In the range of rt145-rt290, rt145, rt221, rt222, rt267, and rt271 were the genotype-polymorphic sites, while rt238 was the genotype-specific sites. Mutations at rt163, rt173, rt180, rt181, rt184, rt191, rt199, and rt214 were more frequent among patients with C-genotype HBV, while those at rt220, rt225, rt226, rt269, and rt274 were more frequent among patients with B-genotype HBV. RtM204V/I could reduce the HBV DNA loads while rtQ/L267H/R could increase the HBV DNA loads. RtV214A/E/I (OR 3.94, 95% CI 1.09 to 14.26) was an independent risk factor for advanced liver diseases. In summary, the hotspots of mutations were different between B and C genotypes. Besides the effect on the S region, RT mutations had effects on HBV replication by other unknown ways. RtV214A/E/I was found to be an independent risk factor for ALD, suggesting that mutations at rt214 site could be used as a potential virological marker for the liver disease progression.
已知 RT 区的突变主要与核苷酸类似物耐药相关。越来越多的研究表明，RT 突变与晚期肝病（ALD）有关，并影响 HBV 复制，但 RT 区突变在肝病发展过程中的分布特征以及 RT 突变对 HBV 复制的影响尚未完全阐明。对 1473 例慢性 HBV 感染患者的 HBV RT 区进行了直接测序。分析突变频率，以确定根据基因型、HBV DNA 载量或肝病进展对组分类别的特定突变。在 rt145-rt290 范围内，rt145、rt221、rt222、rt267 和 rt271 是基因型多态性位点，而 rt238 是基因型特异性位点。rt163、rt173、rt180、rt181、rt184、rt191、rt199 和 rt214 的突变在 C 基因型 HBV 患者中更为常见，而 rt220、rt225、rt226、rt269 和 rt274 的突变在 B 基因型 HBV 患者中更为常见。rtM204V/I 可降低 HBV DNA 载量，而 rtQ/L267H/R 可增加 HBV DNA 载量。rtV214A/E/I（OR 3.94，95%CI 1.09 至 14.26）是晚期肝病的独立危险因素。总之，B 型和 C 型基因型的突变热点不同。除了对 S 区的影响外，RT 突变还通过其他未知途径影响 HBV 复制。发现 rtV214A/E/I 是 ALD 的独立危险因素，提示 rt214 位点的突变可作为肝病进展的潜在病毒学标志物。
