Association Between Single-nucleotide Polymorphisms and Early Spontaneous Hepatitis B Virus E Antigen Seroconversion in Children
Overview
General Medicine
Affiliations
Background: The disease progression following hepatitis B virus (HBV) infection is associated with single-nucleotide polymorphisms (SNPs). However, the role of SNPs in chronic HBV infection in children remains unclear. Here, we investigate the association between SNPs and early spontaneous hepatitis B e antigen (HBeAg) seroconversion in children with chronic hepatitis B infection.
Methods: This was a retrospective cohort study. We genotyped seven SNPs in the following genes, interleukin (IL)-10 (rs1800871 and rs1800872), human leukocyte antigen (HLA)-DPA1 (rs3077), HLA-DPB1 (rs9277535), HLA-DQB2 (rs7453920), HLA-DQB1 (rs2856718), and IL28B (rs8099917), in patients with chronic HBV infection using PCR and sequencing. These variants were analyzed for an association with early HBeAg seroconversion in children.
Results: Of 225 Japanese patients with chronic hepatitis B virus infection (male/female: 105/120, median age at initial visit: 6 years; range 0-44 years), 52 achieved spontaneous HBeAg seroconversion at the age of 10 years or younger (G1: early seroconversion group), and 57 did not achieve spontaneous HBeAg seroconversion under the age of 20 years (G2: late or no seroconversion group). Of the seven SNPs, only the HLA-DPA1 SNP displayed a low p-value (P = 0.070), but not significant, to have early HBeAg seroconversion in the dominant model and in the allele model (P = 0.073) using the chi-square test. The association study found a low p-value, but not significant, to have early HBeAg seroconversion in the dominant model for HLA-DPA1 (genotype TC + TT vs. CC, P = 0.070, odds ratio: 2.016, 95% confidence interval: 0.940-4.323) using a logistic regression model.
Conclusion: Although the HLA-DPA1 SNP did not show a statistically significant association with early HBeAg seroconversion in this study, the HLA-DPA1 SNP might increase the likelihood of achieving early spontaneous HBeAg seroconversion in children.
Tai D, Jeng W, Lin C Hepatol Commun. 2018; 1(10):1005-1013.
PMID: 29404438 PMC: 5721408. DOI: 10.1002/hep4.1113.
Effect of HLA-DPA1 alleles on chronic hepatitis B prognosis and treatment response.
Katrinli S, Enc F, Ozdil K, Ozturk O, Tuncer I, Dinler Doganay G North Clin Istanb. 2017; 3(3):168-174.
PMID: 28275747 PMC: 5336620. DOI: 10.14744/nci.2016.27870.
Hirata M, Kamatani Y, Nagai A, Kiyohara Y, Ninomiya T, Tamakoshi A J Epidemiol. 2017; 27(3S):S9-S21.
PMID: 28190657 PMC: 5363792. DOI: 10.1016/j.je.2016.12.003.
Host Genetic Variants in HLA Loci Influence Risk for Hepatitis B Virus Infection in Children.
Fan J, Huang X, Chen J, Cai Y, Xiong L, Mu L Hepat Mon. 2016; 16(8):e37786.
PMID: 27795724 PMC: 5070562. DOI: 10.5812/hepatmon.37786.
Clinical Relevance of HLA Gene Variants in HBV Infection.
Wang L, Zou Z, Wang K J Immunol Res. 2016; 2016:9069375.
PMID: 27243039 PMC: 4875979. DOI: 10.1155/2016/9069375.