Sci Rep. 2018 Aug 24;8(1):12737. doi: 10.1038/s41598-018-31065-6.
Polymorphisms in the Toll-like receptor 3 (TLR3) gene are associated with the natural course of hepatitis B virus infection in Caucasian population.
Fischer J1, Koukoulioti E2, Schott E3, Fülöp B4, Heyne R5, Berg T2, van Bömmel F2.
Author information
1
Department of Gastroenterology and Rheumatology, Section of Hepatology, University Hospital Leipzig, Leipzig, Germany. [email protected].
2
Department of Gastroenterology and Rheumatology, Section of Hepatology, University Hospital Leipzig, Leipzig, Germany.
3
Department of Gastroenterology, Hepatology and Diabetology, Internal Medicine II, HELIOS Hospital Emil von Behring, Berlin, Germany.
4
Department of Internal Medicine and Gastroenterology, HELIOS Hospital Berlin-Buch, Berlin, Germany.
5
Liver and Study Center Checkpoint, Berlin, Germany.
Abstract
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.