title: CD3Z genetic polymorphism in immune response to hepatitis B vaccination in two independent Chinese populations.
abstract: Vaccination against hepatitis B virus is an effective and routine practice that can prevent infection. However, vaccine-induced immunity to hepatitis B varies among individuals. CD4(+) T helper cells, which play an important role in both cellular and humoral immunity, are involved in the immune response elicited by vaccination. Polymorphisms in the genes involved in stimulating the activation and proliferation of CD4(+) T helper cells may influence the immune response to hepatitis B vaccination. In the first stage of the present study, a total of 111 single nucleotide polymorphisms (SNPs) in 17 genes were analyzed, using the iPLEX MassARRAY system, among 214 high responders and 107 low responders to hepatitis B vaccination. Three SNPs (rs12133337 and rs10918706 in CD3Z, rs10912564 in OX40L) were associated significantly with the immune response to hepatitis B vaccination (P = 0.008, 0.041, and 0.019, respectively). The three SNPs were analyzed further with the TaqMan-MGB or TaqMan-BHQ probe-based real-time polymerase chain reaction in another independent population, which included 1090 high responders and 636 low responders. The minor allele 'C' of rs12133337 continued to show an association with a lower response to hepatitis B vaccination (P = 0.033, odds radio = 1.28, 95% confidence interval = 1.01-1.61). Furthermore, in the stratified analysis for both the first and second populations, the association of the minor allele 'C' of rs12133337 with a lower response to hepatitis B vaccination was more prominent after individuals who were overweight or obese (body mass index ≥25 kg/m(2)) were excluded (1(st) stage: P = 0.003, 2(nd) stage: P = 0.002, P-combined = 9.47e-5). These findings suggest that the rs12133337 polymorphism in the CD3Z gene might affect the immune response to hepatitis B vaccination, and that a lower BMI might increase the contribution of the polymorphism to immunity to hepatitis B vaccination.
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.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Xiao-Pan
authors.initials: XP
authors.lastname: Wu
authors.forename: Xi-Lin
authors.initials: XL
authors.lastname: Zhu
authors.forename: Bing-Yu
authors.initials: BY
authors.lastname: Yan
authors.forename: Jing-Yun
authors.initials: JY
authors.lastname: Li
authors.forename: Ai-Qiang
authors.initials: AQ
authors.lastname: Xu
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Li
mesh_terms: D000328:Adult; D044466:Asian People; D015992:Body Mass Index; D017252:CD3 Complex / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006509:Hepatitis B / Q000276:immunology / Q000517:prevention & control*; D017325:Hepatitis B Vaccines / Q000276:immunology*; D006801:Humans; D007110:Immunity, Active / Q000235:genetics*; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D014611:Vaccination
chemical_list: D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D017325:Hepatitis B Vaccines; D011948:Receptors, Antigen, T-Cell