Association of Toll-like receptor gene polymorphisms with susceptibility to hepatitis B virus-related...

Hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) represents a significant worldwide public health challenge. Toll-like receptors (TLRs) serve as essential components of the innate immune system; however, their involvement as genetic predisposition factors for HBV-ACLF remains incompletely understood. The present investigation aimed to explore the relationship between genetic variants in TLR2, TLR4, and TLR9 and the association with HBV-ACLF (compared to CHB patients). 160 individuals with HBV-ACLF, 280 subjects diagnosed with chronic hepatitis B (CHB), and 280 healthy controls were recruited for this study. Two primary laboratory techniques were utilized in this study. First, serum concentrations of TLR2, TLR4, and TLR9 were assessed using an enzyme-linked immunosorbent assay (ELISA). Second, a PCR-restriction fragment length polymorphism (PCR-RFLP) assay was adopted for the detection of specific genetic variants. HBV-ACLF patients exhibited substantially higher serum concentrations of TLR2, TLR4, and TLR9 than both CHB patients and healthy controls (all p < 0.05). Compared to the CHB control group, two specific polymorphisms emerged as significant risk factors for HBV-ACLF: TLR2 - 196 to - 174 del (D/D genotype: OR = 1.87, 95% CI 1.14-3.05, p = 0.012; D allele: OR = 1.53, 95% CI 1.16-2.03, p = 0.003) and TLR9 rs187084 (C/C genotype: OR = 2.66, 95% CI 1.22-5.78, p = 0.021; C allele: OR = 1.69, 95% CI 1.14-2.50, p = 0.011). The remaining loci showed no meaningful associations (p > 0.05) Elevated serum concentrations of TLRs are observed in individuals diagnosed with HBV-ACLF. Additionally, the TLR2 - 196 to - 174 deletion variant and the TLR9 rs187084 polymorphism demonstrate a robust association with HBV-ACLF when compared to CHB controls. These factors warrant further investigation in prospective cohorts to determine their potential value in predicting disease progression.