Evaluation of the epidemiological significance of molecular genetic factors in relation to the intensity of post-vaccination immunity against hepatitis B

Abstract

Introduction. Hepatitis B retains the status of socially significant infection and remains a major health problem worldwide, including the Russian Federation. The improvement of the effectiveness of the current complex of preventive measures, especially vaccination, is an important task for public health. Although vaccination against hepatitis B is highly successful, 5% to 10% of individuals do not experience a response to vaccine with an adequate level of antibodies to hepatitis B surface antigen (anti-HBs). One of the key factors determining the absence or insufficiency of post-vaccination immunity against hepatitis B may be the single-nucleotide polymorphisms (SNPs) that change gene sequences, including those that determine the mechanism of immunogenesis. Such genetic changes may affect the signaling pathways and result in significant decrease in antibody response to hepatitis B vaccine. Assessment of epidemiological significance of such SNPs is an important task, considering its possible associations with failure to respond adequately to vaccination.The aim of the study was to determine the effect of SNPs of IL1B (rs1143634, rs1143627), IL1RN (rs4251961, rs419598), IL6 (rs1800795), IL10 (rs1800896), TULP1 (rs9380516), TLR4 (rs4986790), MERTK (rs4374383) genes on the formation of post-vaccination immunity against hepatitis B.Materials and methods. Healthcare workers (n = 271) of the Treatment and Rehabilitation Center of the Ministry of Health of the Russian Federation with known vaccination history, data on age, work experience and department of the medical institution were included in this research. The presence and levels of anti-HBs and anti-HBcore IgG antibodies were determined by the ELISA method using the DS-ELISA-ANTI-HBs and DS-ELISA-ANTI-HBc kits, according to the manufacturer’s instructions. Genotyping was performed by real time polymerase chain reaction. Statistical analysis of data was carried out using the "Statistica 6.0" software.Results. Statistically significant differences in the frequencies of CC (rs9380516) genotypes (p = 0.034; OR 0.497; 95% CI 0.261–0.949) and CT (p = 0.044; OR 1.967; 95% CI 1.015–3.812) of the TULP1 gene in the group of individuals with anti-HBs concentrations of 10–100 IU/l were found in association with the intensity of the post-vaccination response against hepatitis B. Also, for this group, differences were found in the structure of the TT/CT genotype pair of IL-10/TULP1 genes (rs1800896/rs9380516) (p = 0.003; OR = 5.39; 95% CI 1.7–17.4) and for the combination of AA/TT SNP MERTK/IL1RN genotypes (rs4374383/rs4251961) (p = 0.003; OR = 7.96; 95% CI 1.7–37.6).Conclusion. Our study revealed that above variants of genotypes could play a role in predicting an increased risk of low (or absence) post-vaccination immune response against hepatitis B. It seems appropriate to use the relationship between the gene polymorphisms and a low concentration of post-vaccination anti-HBs antibodies in assessing scenarios for the development of the epidemic process of hepatitis B, since the identified associations allow to quantify the risks of poor herd immunity against this infection.

Keywords

• single nucleotide polymorphism
• post-vaccination immunity
• hepatitis b
• anti-hbs
• elisa
• pcr