Human Interleukin-10 Genotypes Are Associated with Different Precore/Core Gene Mutation Patterns in Children with Chronic Hepatitis B Virus Infection

• Published in: The Journal of pediatrics 2011-05, Vol.158 (5), p.808-813
• Main Authors: Wu, Jia-Feng, MD, PhD, Ni, Yen-Hsuan, MD, PhD, Lin, Ying-Ting, MS, Lee, Tien-Jui, MS, Hsu, Sandy Huey-Jen, PhD, Chen, Huey-Ling, MD, PhD, Tsuei, Daw-Jen, PhD, Hsu, Hong-Yuan, MD, PhD, Chang, Mei-Hwei, MD
• Format: Article
• Language: English
• Subjects: alanine transaminase; alleles; antiserum; Child, Preschool; children; chronic hepatitis B; Disease Progression; DNA - genetics; Female; Follow-Up Studies; Genotype; hepatitis B antigens; Hepatitis B e Antigens - analysis; Hepatitis B virus; Hepatitis B virus - immunology; Hepatitis B, Chronic - blood; Hepatitis B, Chronic - genetics; Hepatitis B, Chronic - virology; Humans; immunosuppression (physiological); interleukin-10; Interleukin-10 - blood; Interleukin-10 - genetics; Male; Mutation; Pediatrics; Polymerase Chain Reaction; Promoter Regions, Genetic; sequence analysis; seroconversion; Time Factors; Viral Load
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1016/j.jpeds.2010.11.015

Objective To elucidate the association between human interleukin-10 (IL-10) genotypes and hepatitis B virus (HBV) precore/core gene mutation in children with chronic HBV infection. Study design The study group comprised of 21 children with chronic HBV infection with spontaneous hepatitis B e antigen (HBeAg) seroconversion who were followed for more than 10 years. Another nine children without HBeAg seroconversion served as the control subjects. Sera at the immune tolerance and inflammatory phase (alanine aminotransferase, >80 IU/L) were subjected to HBV precore/core sequence analysis. IL-10 -1082 polymorphism was also determined. Results HBV precore/core gene mutation increased significantly more in the inflammatory phase than in the tolerance phase (G1896A, 76.2% versus 4.8%; C1913A, 33.3% versus 0%; C2189A, 28.6% versus 4.8%; G2304A, 52.4% versus 14.3%) in study group (n = 21) but not the control group (n = 9). Subjects with the G/G genotype at the IL-10-1082 polymorphism site had higher C2189A mutation rate than the A allele carriers ( P = .02). C2189A mutation carriers are associated with more viral load decrement from tolerance to inflammatory phase ( P = .01) and earlier spontaneous HBeAg seroconversion ( P = .01). Conclusions The G/G genotype at the IL-10 -1082 polymorphism is associated with higher C2189A mutations, lower HBV viral load at immune inflammatory phase, and earlier spontaneous HBeAg seroconversion than A allele carriers.