Clinical significance and mutation characteristics in the core promoter/pre-C region of different HBV genotypes in children

Abstract

Objective: To understand the clinical significance and mutation characteristics in the basic core promoters and pre-C region (BCP/PC) of different hepatitis B virus genotypes samples of infected children. Methods: A total of 294 children and 92 adults with CHB infection who were treated at four hospitals in Chongqing from 2011 to 2018 were collected. The BCP / PC region of HBV was amplified by PCR and sequenced directly to comparatively analyze the gene mutation conditions in this region. The two sample means were compared by the t-test, and the nonparametric data was compared by Wilcoxon-Mann-Whitney test. χ2 test or Fisher's exact test was used to compare the data rates of the two groups. Results: Children and adult patients were dominated by genotype B; accounting for 76.9% and 71.7%, respectively, and genotype C accounted for 23.1% and 28.3%, respectively. In the children group, the mutation rates of ten nucleotide sites containing nt 1679, 1721, 1753, 1757, 1758, 1762, 1764, 1775, 1856 and 1858 of the genotype C samples was significantly higher than that of genotype B samples. The mutation rates of G1721a, C1856t and T1858c of genotype C samples were 30.9%, 16.2% and 30.9%, respectively, while the mutation rates of genotype B samples were 0.4%, 0, 0, P < 0.001, respectively. In the adult group, the only three sites containing nt 1679, 1758, and 1775 of the genotype C sample had a higher mutation rate than the genotype B samples. The combined mutations pattern were only detected in children with genotype C samples, but not in children and adult with genotype B samples. Further analysis showed that the age of G1721A/A1775G/T1858C containing combined mutation group was significantly lower than that of the non-mutation group [(4.58 ± 2.53) years vs. (6.53 ± 4.02) years, P = 0.012]. Serum HBV DNA titer was significantly higher in combined mutation group than that of the non-mutation group [(7.57 ± 2.03) log10 copies / ml vs. (6.61 ± 2.11) log10 copies / ml, P = 0.045]. Conclusion: The frequencies of mutations in the BCP/PC region of HBV-infected children in genotype C samples were significantly higher than that of genotype B samples. Genotype-related combined site mutations were only found in children with genotype C samples, and were also associated with younger patients and high HBV-DNA titers.