title: Polymorphisms in IRG1 gene associated with immune responses to hepatitis B vaccination in a Chinese Han population and function to restrain the HBV life cycle.
abstract: Vaccination against the hepatitis B virus (HBV) is extensively used as an effective method to prevent HBV infection. However, nearly 10% of healthy adults fail to produce a protective level of antibodies against the hepatitis B vaccine, and multiple genetic variants are known to affect the immune response to the hepatitis B vaccine. The aim of the present study was to investigate the association between polymorphisms in immunoresponsive gene 1 (IRG1) gene and the immune response to hepatitis B vaccination in a Chinese Han population. Four single nucleotide polymorphisms (SNPs) located in the IRG1 gene were genotyped in 1230 high-responders and 451 non-responders to hepatitis B vaccination. The SNPs rs17470171 and rs17385627 were associated with the immune response to hepatitis B vaccination (P = 0.014 and 0.029, respectively). In addition, the haplotypes G-A-A-A (rs614171-rs17470171-rs9530614-rs17385627, P = 0.0042, OR = 0.68) and A-A (rs17470171-rs17385627, P = 0.0065, OR = 0.72) exerted a protective role in the immune response to hepatitis B vaccination. Allele 'A' of rs17470171 and allele 'A' of rs17385627 show higher levels of expression for the IRG1 gene compared with allele 'C' of rs17470171 and allele 'T' of rs17385627 as demonstrated by luciferase reporter and overexpression assays. In addition, we observed that IRG1 inhibited the HBV life cycle and that IRG1 rs17385627 allele 'A' was more effective than rs17385627 allele 'T' at eliminating HBV in HepG2.2.15 cells. These findings suggest that polymorphisms in the IRG1 gene are associated with the immune response to hepatitis B vaccination. The antiviral effect of IRG1 was confirmed using HBV infection cell models.
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Shandong Center for Disease Control and Prevention, Jinan, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Xiao-Pan
authors.initials: XP
authors.lastname: Wu
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Xi-Lin
authors.initials: XL
authors.lastname: Zhu
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Pan
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Shandong Center for Disease Control and Prevention, Jinan, China.
authors.forename: Bing-Yu
authors.initials: BY
authors.lastname: Yan
authors.affiliation: Shandong Center for Disease Control and Prevention, Jinan, China.
authors.forename: Ai-Qiang
authors.initials: AQ
authors.lastname: Xu
authors.affiliation: Department of Epidemiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People; D002262:Carboxy-Lyases; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology; D005838:Genotype; D006239:Haplotypes; D056945:Hep G2 Cells; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000208:ethnology / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*
chemical_list: D017325:Hepatitis B Vaccines; D011506:Proteins; C561544:ACOD1 protein, human; D002262:Carboxy-Lyases
keywords: HBV infectionIRG1; antiviral; hepatitis B vaccination; immune response; polymorphism