Abstract
Toll-like receptors (TLRs) play a key role in innate and adaptive immunity, protecting the host from viral pathogens. We studied the effect of TLR7 polymorphisms on disease susceptibility and progression of chronic hepatitis B (CHB) infection in Chinese adults. Blood samples were taken from 612 patients with confirmed CHB, hepatitis B virus (HBV)-related liver cirrhosis (LC) or hepatocellular carcinoma (HCC) and 293 controls. TLR7 polymorphisms (rs179010-C > T, rs2074109-T > C, and rs179009-A > G) were analyzed by PCR-based sequencing. A significantly higher frequency of TLR7 rs179010 C allele was found in male CHB patients than in controls (74.8% vs 59.5%, P = 0.002). The frequency of rs179009 G allele was markedly increased with disease progression when male patients with CHB, LC and HCC were compared (P = 0.012). The haplotype CTA was significantly associated with an increased susceptibility to CHB among male patients (P = 0.000). Frequency of the haplotype CTG was higher in male patients with HCC than CHB (P = 0.005). No such differences in these allele frequencies were found between female patients and controls. Our results indicated that TLR7 polymorphisms play an important role in disease susceptibility and the progression of CHB infections in Chinese adults, and may partly explain the high incidence of HBV related diseases in Chinese men.
Highlights
Hepatitis B virus (HBV) infection is a global health problem[1]
We aimed to explore the relationship between these three TLR7 polymorphisms and hepatitis B virus (HBV)-related liver diseases in the Chinese Han population to gain a better understanding of the role of TLR7 in the development of HBV infection
HBV-DNA copies were significantly decreased from chronic hepatitis B (CHB) to liver cirrhosis (LC) and hepatocellular carcinoma (HCC) (P < 0.001)
Summary
Hepatitis B virus (HBV) infection is a global health problem[1]. HBV carriers are at an increased risk of liver damage and many of them suffer from progressive liver diseases, such as chronic hepatitis B infection (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC)[2]. Studies indicated that HBV could not efficiently induce a TLR-mediated immune response, resulting in the lack of type I IFN release in its natural hosts during early phase of infection[12], the virus can possibly activate TLR pathways in infected hepatocytes and nonparenchymal liver cells to limit viral replication[10]. Wang et al found that the polymorphism of TLR7 rs179009 might impair immune responses during HCV infection among the Chinese population[22]. The minor allele frequency of rs2074109 is 0.099 in Japanese and 0.069 in Chinese Han populations, highest among all other populations reported in the 1000 genomes study[24] The effect of this SNP on health and disease has been not reported. We aimed to explore the relationship between these three TLR7 polymorphisms and HBV-related liver diseases in the Chinese Han population to gain a better understanding of the role of TLR7 in the development of HBV infection
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