Toll-like receptors and cytokines/cytokine receptors polymorphisms associate with non-response to hepatitis B vaccine.

It is well documented that 5-10% hepatitis B adult vaccinees are non- and hypo-responders and probably are not adequately protected against hepatitis B virus (HBV) infection. The sequence variations of genes involved in processes such as pathogen recognition, antigen processing and presentation, and differentiation/maturation of lymphocytes may affect the duration and intensity of protective humoral immune response to the hepatitis B vaccine. In this study, frequencies of 53 known SNPs within 21 candidate genes were analyzed among 46 responders and 24 non-responders. Four SNPs (rs2243248, rs1805015, rs1295686 and rs3804100) in IL-4, IL-4RA, IL-13 and TLR2 genes were found significantly associated with the vaccinees' status of serum anti-HBV response triggered by the vaccine (P<0.05). Two SNPs (rs1295686 and rs1805015) also showed significant association with the vaccine-induced immune response when analyzed together with risk factors such as age and gender, by multivariable logistic regression analysis (P<0.05). Further, haplotype analysis showed that the AG haplotype defined by SNPs rs1143633 (IL-1B; intron) and rs1143627 (IL-1B; intron) was present more frequently in non-responders than in responders (P=0.035). Thus, specific SNPs in genes of cytokines/cytokine receptors and TLR2 were associated with status of the hepatitis B vaccine-induced protective humoral immune response.