Polymorphisms in the Toll-like receptor 3 (TLR3) gene are associated with the natural course of hepatitis B virus infection in Caucasian population
Polymorphisms in the Toll-like receptor 3 (TLR3) gene are associated with the natural course of hepatitis B virus infection in Caucasian population
复制标题
DOI：
10.1038/s41598-018-31065-6
复制
发表时间：
2018-08-24
影响因子：
4.6
通讯作者：
van Boemmel, Florian
中科院分区：
文献类型：
--
作者：
Fischer, Janett;Koukoulioti, Eleni;van Boemmel, Florian
先天免疫可诱导乙型肝炎病毒（HBV）感染的乙型肝炎表面抗原（HBsAg）自发性血清清除（SC）或向无活性载体状态转变。toll样受体（TLR） 3信号传导与这些过程有关。TLR3基因的改变可能会损害对HBV的免疫反应。在我们的研究中，我们分析了TLR3多态性rs3775291和rs5743305对HBV感染自然过程的影响。在这项回顾性研究中，研究人员招募了621名慢性HBV感染（CHB）患者、239名自发性HBsAg SC患者和254名健康对照者。在CHB组中，49%的患者为非活性携带者，17%为hbeag阳性。TLR3 rs3775291A等位基因与自发性HBsAg SC和HBeAg SC的可能性降低以及发生慢性乙型肝炎的风险增加相关。在单倍型分析中，包括风险变体rs3775291A和rs5743305A的单倍型发生HBsAg SC的可能性最低，需要进一步的大队列研究和功能分析来阐明TLR3信号的影响。
Innate immunity can induce spontaneous hepatitis B surface antigen (HBsAg) seroclearance (SC) of hepatitis B virus (HBV) infection or transition towards an inactive carrier state. Toll-like receptor (TLR) 3 signalling has been linked to these processes. Alterations in the TLR3 gene might impair immune responses against HBV. In our study, we analysed the impact of the TLR3 polymorphisms rs3775291 and rs5743305 on the natural course of HBV infection. In this retrospective study, a Caucasian cohort of 621 patients with chronic HBV infection (CHB), 239 individuals with spontaneous HBsAg SC, and 254 healthy controls were enrolled. In the CHB group, 49% of patients were inactive carriers, and 17% were HBeAg-positive. The TLR3 rs3775291 A allele was associated with a reduced likelihood of spontaneous HBsAg SC and HBeAg SC, and an increased risk of developing chronic hepatitis B. In haplotype analysis, the haplotype including both risk variants rs3775291A and rs5743305A had the lowest likelihood of HBsAg SC. Further research in larger cohorts and functional analyses are needed to shed light on the impact of TLR3 signalling.