Associations of toll-like receptor 4, 5 and 9 genetic variants with hepatitis B virus-related hepatocellular carcinoma and viral clearance in a Guangxi male population

Toll-like receptors 4, 5 and 9 (TLR4, 5 and 9) are involved in the induction of innate immune response against hepatitis B virus (HBV) infection. This study aimed to explore the potential role of TLR4, 5 and 9 polymorphisms in the susceptibility to HBV clearance and HBV-related hepatocellular carcinoma (HCC). In this study, five single nucleotide polymorphisms (SNPs) (rs1927911, rs11536889, rs10759930, rs10983755 and rs2149356) at the TLR4 gene, one SNP (rs5744174) at the TLR5 gene and two SNPs at the TLR9 gene (rs187084 and rs352140) were genotyped in 395 patients with HBV-positive HCC, 293 with persistent HBV carriers and 686 with HBV natural clearance subjects. In the case of TLR5 rs5744174, the GA genotype (heterozygote model: adjusted OR=0.67; 95% CI, 0.50-0.90; P=0.008) and GA+GG genotype (dominant model: adjusted OR=0.67; 95% CI, 0.51-0.89; P=0.006) carriers were associated with HBV clearance as compared to the AA genotype carriers. In the case of TLR4 rs10983755, the AA genotype carriers were associated with HBV clearance as compared to the AG+GG genotype (recessive model: adjusted OR=0.39; 95% CI, 0.16-0.94; P=0.036) and GG genotype (homozygote model: adjusted OR=0.39; 95% CI, 0.16-0.93; P=0.034) carriers. All other SNPs showed no significant associations with HBV-positive HCC and HBV natural clearance. These results demonstrated that SNP rs10983755 in TLR4 and SNP rs5744174 in TLR5 were associated with HBV natural clearance, and may be risk factors for HBV clearance.