title: Association of the interleukin-12 polymorphic variants with the development of antibodies to surface antigen of hepatitis B virus in hemodialysis patients in response to vaccination or infection.
abstract: Cytokines, involved in the T-helper 1 system, play a role in the regulation of hepatitis B virus (HBV) clearance and the immune response to HBV antigens during natural infection or planned vaccination. Our aim was to examine whether the polymorphic variants of IL-12 are equally associated with development of antibodies to HBV surface antigen (anti-HBs) in hemodialysis (HD) patients in the case of HBV vaccination or HBV infection. The IL-12A rs568408 and IL-12B rs3212227 polymorphisms were analyzed in relation to anti-HBs development in 602 HD patients with negative antibodies to HBV core antigen (anti-HBc) who were hepatitis B vaccinated (group I) as well as in 237 anti-HBc positive HD patients who were infected with HBV in the past (group II). In group I, 199 patients did not develop an anti-HBs titre >10 IU/L (subgroup Ia), whereas in group II, 55 patients did not develop an anti-HBs titre >10 IU/L (subgroup IIa). Patients of groups I and II that developed an anti-HBs >10 IU/L were included into subgroups Ib and IIb, respectively. In hepatitis B vaccinated HD patients, development of a protective anti-HBs titre was positively associated with vintage of renal replacement therapy (RRT), chronic glomerulonephritis as a cause of RRT, and GA rs 568408 IL-12A (OR 1.6, 95 % CI 1.0-2.5, P = 0.035), but a frequency distribution of this genotype between responders and non-responders was not significant when the Bonferroni correction was applied. In HBV infected HD patients, anti-HBs development was positively associated with AC rs3212227 IL-12B (OR 8.0, 95 % CI 2.6-24.9, P < 0.001), whereas HBsAg positivity, AA rs3212227 IL-12B (OR 0.3, 95 % CI 0.1-0.7, P = 0.007), and CC rs3212227 IL-12B (OR 0.1, 95 % CI 0.03-0.6, P = 0.011) were negative predictors of positive anti-HBs phenotype. When the Bonferroni correction was applied, if appropriate, these associations remained significant. In HD patients, the studied IL-12 polymorphic variants seem to be associated with the anti-HBs phenotype (a) with borderline significance for IL-12A in hepatitis B vaccinated patients, and (b) significantly for IL-12B in patients who underwent natural HBV infection.
authors.affiliation: Department of Nephrology, Transplantology and Internal Diseases, Poznań University of Medical Sciences, 49 Przybyszewskiego Blvd, 60-355, Poznań, Poland, alicja_grzegorzewska@yahoo.com.
authors.forename: Alicja E
authors.initials: AE
authors.lastname: Grzegorzewska
authors.forename: Piotr M
authors.initials: PM
authors.lastname: Wobszal
authors.forename: Anna
authors.initials: A
authors.lastname: Sowińska
authors.forename: Adrianna
authors.initials: A
authors.lastname: Mostowska
authors.forename: Paweł P
authors.initials: PP
authors.lastname: Jagodziński
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003710:Demography; D005260:Female; D056726:Genetic Association Studies; D006509:Hepatitis B / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D006510:Hepatitis B Antibodies / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D053765:Interleukin-12 Subunit p35 / Q000235:genetics*; D053762:Interleukin-12 Subunit p40 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D006435:Renal Dialysis; D014611:Vaccination; D055815:Young Adult
chemical_list: D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; C508858:IL12A protein, human; C500879:IL12B protein, human; D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40