Polymorphisms in the Vitamin A Receptor and Innate Immunity Genes Influence the Antibody Response to Rubella Vaccination

• Published in: The Journal of infectious diseases 2010-01, Vol.201 (2), p.207-213
• Main Authors: Ovsyannikova, Inna G., Haralambieva, Iana H., Dhiman, Neelam, O'Byrne, Megan M., Pankratz, V. Shane, Jacobson, Robert M., Poland, Gregory A.
• Format: Article
• Language: English
• Subjects: Adolescent; Alleles; Antibodies; Antibodies, Viral - genetics; Antibody Formation; Antiviral Restriction Factors; Biological and medical sciences; Carrier Proteins - genetics; Child; DEAD Box Protein 58; DEAD-box RNA Helicases - genetics; Female; Fundamental and applied biological sciences. Psychology; Genes; Genotype; Human viral diseases; Humans; Immunity; Immunity, Innate - genetics; Infectious diseases; Innate immunity; Male; Medical sciences; Microbiology; Minor Histocompatibility Antigens; Polymorphism, Single Nucleotide; Receptors; Receptors, Immunologic; Repressor Proteins - genetics; Rubella; Rubella Vaccine - immunology; Tripartite Motif Proteins; Ubiquitin-Protein Ligases; Vaccination; Viral diseases; Viral diseases with cutaneous or mucosal lesions and viral diseases of the eye; VIRUSES; Vitamin A; Young Adult
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/649588

Background. Genetic polymorphisms play an important role in rubella vaccine-induced immunity. Methods. We genotyped 714 healthy children after 2 age-appropriate doses of rubella-containing vaccine for 142 potential single-nucleotide polymorphisms (SNPs). Results.Specific polymorphisms in the vitamin A receptor, retinoic acid-inducible gene I (RIG-I), and tripartite motif 5 and 22 (TRIM5 and TRIM22) genes were significantly associated with rubella vaccine humoral immunity. The minor allele of the rs4416353 in the vitamin A receptor gene was associated with an allele dose—related decrease (P = .019) in rubella antibody response. The minor allele of rs6793694, in the vitamin A receptor gene, was associated with an allele dose—related antibody decrease (P = .039). The minor variant ofnonsynonymous SNP rs10813831 (Arg7Cys) in the RIG-I gene was associated with an allele dose—related decrease in rubella antibody level from 37.4 to 28.0 IU/mL (P = .035), whereas increased representation of the minor allele of the 5'UTR SNP (rs3824949, P = .015) in the antiretroviral TRIM5 gene was associated with an allele dose—related increase in rubella antibody. It is of particular interest that the nonsynonymous SNP rs3740996 (His43Tyr) in the TRIM5 gene was associated with variations in rubella antibody response (P = .016) after having been previously found to play a significant functional role. Conclusions. These findings further expand our immunogenetic understanding of mechanisms of rubella vaccine—induced immunity.