title: Family study of non-responsiveness to hepatitis B vaccine confirms the importance of HLA class III C4A locus.
abstract: Non-responsiveness to hepatitis B virus (HBV) vaccine in adults is strongly associated with HLA-C4AQ0,DRB1*0301,DQB1*02 haplotype. This association was also demonstrated in neonates who failed to mount a humoral response to challenge with HBV vaccine. About 4% of vaccinated newborns do not reach a protective antibody level (> or =10 mIU/ml) at seroconversion and 0.4% is a non-responder even after receiving a fourth dose of vaccine (true non-responders (TNR)); while 3.6% achieved an antibody level > or =10 mIU/ml (slow responders (SR)) only when reboostered with the fourth dose. In the present study we extend the vaccination and HLA typing to 91 family members of probands to understand better the possible parent-to-child transmission of this trait. A transmission disequilibrium test (TDT), performed in 27 families, showed that the C4AQ0 allele was almost always transmitted to probands, both TNRs and SRs. Although not statistically significant, the highest LOD score was obtained with C4A locus: 1.58. These results suggest the presence of a region regulating immune response against HBV vaccination near to or coincident with the C4A locus.
authors.affiliation: Unità di Biometria, Dipartimento di Genetica e Microbiologia-Università di Pavia, Via Abbiategrasso 207, Pavia, Italy. de_silvestri_annalisa@hotmail.com
authors.forename: A
authors.initials: A
authors.lastname: De Silvestri
authors.forename: A
authors.initials: A
authors.lastname: Pasi
authors.forename: M
authors.initials: M
authors.lastname: Martinetti
authors.forename: C
authors.initials: C
authors.lastname: Belloni
authors.forename: C
authors.initials: C
authors.lastname: Tinelli
authors.forename: G
authors.initials: G
authors.lastname: Rondini
authors.forename: L
authors.initials: L
authors.lastname: Salvaneschi
authors.forename: M
authors.initials: M
authors.lastname: Cuccia
mesh_terms: D000483:Alleles; D005260:Female; D015236:HLA-C Antigens / Q000032:analysis / Q000235:genetics* / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000276:immunology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015810:Linkage Disequilibrium / Q000235:genetics; D008126:Lod Score; D008297:Male; D010375:Pedigree
chemical_list: D015236:HLA-C Antigens; D017325:Hepatitis B Vaccines