Association Of Cytokine And HLA Gene Polymorphisms With Long-term Humoral Response In Children Vaccinated Against Hepatitis B In Infancy

Section I Association of cytokine gene polymorphisms with long-term humoral response in children vaccinated against hepatitis B in infancyObjective To investigate the relationship between cytokine gene polymorphisms and long-term humoral response in children vaccinated against hepatitis B during infancy.Methods A total of293children (6.08±0.59years old) who received three doses of hepatitis B vaccine according to a0-,1-,6-month schedule during infancy and were negative for HBsAg and/or anti-HBc, were enrolled. Of them,83children with anti-HBs<10mIU/ml were considered as long-term non-and hypo-responders, and210others with anti-HBs≥10mIU/ml were defined as long-term responders. A total of11single nucleotide polymorphisms (SNPs) of IL-1β, IL-2, IL-4, IL-10, IL-12B, and IL-13were detected with PCR-restriction fragment length polymorphism, and the SNPs were verified by DNA sequencing.Results The allele frequencies of-33T,-589T, and2979T in IL-4gene in long-term non-and hypo-responders were86.1%,86.1%and90.4%, respectively, higher than those in long-term responders (76.0%,76.9%, and83.3%, respectively, all P<0.05). In IL-4gene, frequencies of TT genotype at position-33and-589in long-term non-and hypo-responders were74.7%and75.9%respectively, higher than those in long-term responders (57.1%and59.0%respectively, both P<0.01), while the frequencies of CT at position-33and-589in long-term non-and hypo-responders were22.9%and20.5%respectively, lower than those in long-term responders (37.6% and35.7%respectively, both P<0.05). The genotype distributions of IL-42979and the allele or genotype distributions of8other SNPs showed no significant differences between long-term non-and hypo-responders and responders.Conclusions Polymorphisms at position-33,-589, and2979in IL-4gene are associated with the long-term humoral response in children vaccinated against hepatitis B during infancy. Section ⅡAssociation of human leukocyte antigen gene polymorphisms with long-term humoral response in children vaccinated against hepatitis B in infancyObjective To investigate the relationship between the human leukocyte antigens class ⅡDR (DRB1*01, DRB1*03, DRB1*04, DRB1*07, DRB1*08, DRB1*11, DRB1*1301/1302) and DQ (DQB1*0201, DQB1*0401, DQB1*0501) subregions gene polymorphisms and long-term humoral response in children vaccinated against hepatitis B during infancy.Methods A total of297children, who were born in2003and2004, and immunized with recombinant (yeast) hepatitis B vaccine (5μg) at0,1,6months during infancy respectively, were enrolled. Blood samples were collected from the children during October2009through March2010. All the children were were negative for HBsAg and/or anti-HBc. Of them,86children with anti-HBs <10mIU/ml were considered as long-term non-and hypo-responders, and211others with anti-HBs≥10mIU/ml were defined as long-term responders. A total of ten alleles in DR and DQ subregions were detected with polymerase chain reaction sequence-specific primers. The chi-square (χ2) test was used to examine the differences of each allele between long-term non-and hypo-responders and responders.Results There was no significant difference in gender or age between the long-term non-and hypo-responders and responders (P=0.20, P=0.87; respectivly). Although no statistically significant differences were found between long-term non-and hypo-responders and responders at5%leve, the frequencies of HLA-DRB1*04and DRB1*07in long-term non-and hypo-responders were27.1%and36.0%, respectively, higher than those in responders (18.5%and27.0%); while the frequencies of HLA-DQB1*0401in long-term non-and hypo-responders were significant higher than those in responders (15.1%and7.6%respectively, OR=2.17,95%CI=1.0-4.73, P=0.047). The allele distributions of5other alleles in DR subregion and2other alleles in DQ subregion between long-term non-and hypo-responders and responders were similar.Conclusions HLA-DQB1*0401is associated with the long-term humoral response in children vaccinated against hepatitis B during infancy.