title: Effects of cytokine and cytokine receptor gene variation on high anti-HB titers: following up on Taiwan's neonatal hepatitis B immunization program.
abstract: BACKGROUND
  A significant percentage of Taiwanese neonatal HB immunization recipients have subsequently exhibited low anti-HB titers at non-protective or undetectable levels. Several mechanisms have been proposed to explain this phenomenon, including low vaccination responsiveness, deficient lymphocyte function, inappropriate antigen processing and presentation, and abnormal cytokine secretion.
  
  
  METHODS
  To determine genetic influences resulting in high anti-HB titers, we divided a study cohort of 183 individuals into an anti-HBs≥1000 mIU/mL group and a 10-1000 mIU/mL anti-HBs titer group. Chi-square tests were used to compare genotype and allelic frequencies between the two groups.
  
  
  RESULTS
  Data from univariate and multivariate regression analyses of cytokine and cytokine receptor gene variants indicate (a) increased potential of high anti-HB titers in the presence of the TT genotype of the IL-4 rs2243250 SNP (OR=3.19; p=0.012) and the AA genotype of the IL-4R rs1805010 SNP (OR=2.25; p=0.048), and (b) individuals carrying the TT genotype of the IL-4 rs2243250 SNP had anti-HB titers at levels that were almost twice as high as those in individuals carrying the CC genotype (478.8 mIU/mL and 290.3 mIU/mL, respectively; p=0.033).
  
  
  CONCLUSIONS
  Genetic determinants, especially IL-4 and IL-4R, may contribute to high anti-HB titers in immune responses to HB vaccinations.
authors.affiliation: Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Ying-Ju
authors.initials: YJ
authors.lastname: Lin
authors.forename: Yu-Ching
authors.initials: YC
authors.lastname: Lan
authors.forename: Yu-Chuen
authors.initials: YC
authors.lastname: Huang
authors.forename: Ting-Hsu
authors.initials: TH
authors.lastname: Lin
authors.forename: Shao-Mei
authors.initials: SM
authors.lastname: Huang
authors.forename: Chien-Chen
authors.initials: CC
authors.lastname: Lai
authors.forename: Chiu-Shong
authors.initials: CS
authors.lastname: Liu
authors.forename: Cheng-Wen
authors.initials: CW
authors.lastname: Lin
authors.forename: Shih-Yin
authors.initials: SY
authors.lastname: Chen
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
mesh_terms: D000293:Adolescent; D044466:Asian People; D015331:Cohort Studies; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D005787:Gene Frequency; D005838:Genotype; D006510:Hepatitis B Antibodies / Q000235:genetics / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000276:immunology*; D006801:Humans; D017589:Immunization Programs; D007223:Infant; D015847:Interleukin-4 / Q000235:genetics* / Q000276:immunology; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D019948:Receptors, Interleukin-4 / Q000235:genetics* / Q000276:immunology; D013624:Taiwan; D055815:Young Adult
chemical_list: D016207:Cytokines; D006510:Hepatitis B Antibodies; D017325:Hepatitis B Vaccines; C508598:IL4 protein, human; D019948:Receptors, Interleukin-4; D015847:Interleukin-4