Association of polymorphisms of cytokine and TLR-2 genes with long-term immunity to hepatitis B in children vaccinated early in life

Vaccine. 2012 Aug 24;30(39):5708-13. doi: 10.1016/j.vaccine.2012.07.010. Epub 2012 Jul 20.

Abstract

Hepatitis B vaccine is effective in preventing hepatitis B virus (HBV) infection. However, 5-10% of vaccinees fail to produce sufficient antibody against hepatitis B surface antigen (anti-HBs). In this study, we investigated the association of genetic polymorphisms with long-term response to hepatitis B vaccine in 301 children who received the vaccine 5-7 years ago. Of them, 86 (28.6%) had anti-HBs <10 mIU/ml (group A) and 215 (71.4%) had anti-HBs ≥10 mIU/ml (group B). While the frequencies of T allele and TT genotype in single nucleotide polymorphisms (SNP) rs2243250 and rs2070874 of interleukin (IL)-4 in group A were higher than those in group B (all P<0.05 and q<0.2), the frequency of C allele in SNP rs2243250, rs2070874 and rs2227284 of IL-4 in group B was higher than that in group A (all P<0.05 and q<0.2). None of 11 other SNP in IL-2, IL-10, IL-1β, IL-13, IL-12B, tumor necrosis factor-α, and toll-like receptor-2 genes was found to associate with anti-HBs response. SNP rs2070874 was associated with humoral response to hepatitis B vaccine after analyzed by multivariable logistic regression analysis (P=0.015). The haplotype TT defined by SNP rs2243250 and rs2070874 in IL-4 was associated with the poor humoral response (adjusted P=0.037). Our findings demonstrate that IL-4 gene polymorphisms may affect the long-term immune response to hepatitis B vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Child, Preschool
  • Cytokines / genetics
  • Female
  • Haplotypes
  • Hepatitis B / immunology*
  • Hepatitis B / prevention & control
  • Hepatitis B Antibodies / blood
  • Hepatitis B Surface Antigens / immunology
  • Hepatitis B Vaccines*
  • Humans
  • Immunity, Humoral
  • Immunologic Memory
  • Interleukin-4 / genetics*
  • Male
  • Polymorphism, Single Nucleotide*
  • Toll-Like Receptor 2 / genetics*

Substances

  • Cytokines
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • Hepatitis B Vaccines
  • IL4 protein, human
  • TLR2 protein, human
  • Toll-Like Receptor 2
  • Interleukin-4