Background and aims: Chemokine (C-X-C motif) ligand 10 (CXCL10) has been recently shown to be associated with inflammatory diseases. However, the association between the genetic variation of this gene and the susceptibility to hepatitis B virus (HBV) infection remains unclear, especially in children. This study aimed to investigate the relationship between CXCL10 polymorphisms and the risk of chronic HBV infection in a Chinese Han population.
Methods: A two-stage case-control study of 1048 adults and 627 children was performed. A total of 5 tagging SNPs in CXCL10 were genotyped. Dual-Luciferase Reporter Assay was used to assess the effect of the rs4508917 polymorphism on transcriptional activity of CXCL10.
Results: CXCL10 rs4508917 and rs4256246 polymorphisms were significantly associated with an increased risk of chronic HBV infection in Chinese Han adults (p = 0.036 and p = 0.033), of which rs4508917 AA genotype could increase the serum CXCL10 level (p = 0.014). In addition, the rs4508917 AA genotype was identified to facilitate HBV persistent infection (p = 0.017) and breakthrough infection (p = 0.013) in children. Subsequent functional analysis indicated that rs4508917 A allele could promote the transcriptional activity of CXCL10. Additionally, we observed that the rs4508917 A allele carriers (AA and AG genotypes) had a limited HBV viral load suppression in patients treated with nucleos(t)ide analogues (NAs).
Conclusion: The A allele of the CXCL10 rs4508917 may be a risk factor of the persistent HBV infection both in adults and children, which may influence the response to NAs treatment.
Keywords: Chemokine C-X-C motif ligand 10; Hepatitis B virus; Single nucleotide polymorphism.
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