Association of DNA methylation of IFNG gene with no/low response to hepatitis B vaccine in children

Abstract

Objective: To explore the association of DNA methylation with immune response to hepatitis B (HepB) vaccine in Han nationality children from Guangxi province. Methods: A total of 263 children aged 8-9 months who had completed HepB immunization program were recruited from three hospitals in Guangxi province by using unmatched case-control method. Children with the HepB surface antibody concentration(Anti-HBs)<100 mIU/ml was set as the case group and ≥100 mIU/ml as the control group. Multiplex PCR and heavy sulfite sequencing were used to treat the samples. Illumina platform was used for high-throughput DNA methylation sequencing of IFNG gene target regions and CpG sites. Unconditional logistic regression was used to analyze the association between cytosine-phospho-guanosine DNA methylation at 18 loci of IFNG gene and HepB immune response level. Results: There were 104 children in the case group and 159 in the control group. The median (Q1, Q3) level of anti-HBs in two groups were 62.34 (30.06, 98.88) mIU/ml and 1 089.10 (710.35, 1 233.45) mIU/ml. The methylation levels of IFNG_1 gene 44 and 93 locus in the case group were higher than those in the control group (P<0.05). The unconditional logistic regression model showed that the DNA methylation level of IFNG_1 gene at 44 (OR=1.18, 95%CI: 1.03-1.35) and 93 (OR=1.21, 95%CI: 1.07-1.38) locus was associated with the HepB response level. Conclusion: The changes of DNA methylation at locus 44 and 93 of IFNG_1 gene may be relevant factors affecting the response level of HepB in Han nationality children from Guangxi province.