Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Apr;71(4):383-91.
doi: 10.1016/j.humimm.2010.01.004. Epub 2010 Jan 31.

2'-5'-Oligoadenylate synthetase single-nucleotide polymorphisms and haplotypes are associated with variations in immune responses to rubella vaccine

Iana H Haralambieva  1 , Neelam Dhiman, Inna G Ovsyannikova, Robert A Vierkant, V Shane Pankratz, Robert M Jacobson, Gregory A Poland
Affiliations

2'-5'-Oligoadenylate synthetase single-nucleotide polymorphisms and haplotypes are associated with variations in immune responses to rubella vaccine

Iana H Haralambieva et al. Hum Immunol. 2010 Apr.

Abstract

Interferon-induced antiviral genes are crucial players in innate antiviral defense and potential determinants of immune response heterogeneity. We selected 114 candidate single-nucleotide polymorphisms (SNPs) from 12 antiviral genes using an LD tagSNP selection approach and genotyped them in a cohort of 738 school children immunized with two doses of rubella vaccine. Associations between SNPs/haplotypes and rubella virus-specific immune measures were assessed using linear regression methodologies. We identified 23 significant associations (p < 0.05) between polymorphisms within the 2'-5'-oligoadenylate synthetase (OAS) gene cluster, and rubella virus-specific IL-2, IL-10, IL-6 secretion, and antibody levels. The minor allele variants of three OAS1 SNPs (rs3741981/Ser162Gly, rs1051042/Thr361Arg, rs2660), located in a linkage disequilibrium block of functional importance, were significantly associated with an increase in rubella virus-specific IL-2/T(h)1 response (p <or = 0.024). Seven OAS1 and OAS3 promoter/regulatory SNPs were similarly associated with IL-2 secretion. Importantly, two SNPs (rs3741981 and rs10774670) independently cross-regulated rubella virus-specific IL-10 secretion levels (p < or = 0.031). Furthermore, both global tests and individual haplotype analyses revealed significant associations between OAS1 haplotypes and rubella virus-specific cytokine secretion. Our results suggest that innate immunity and OAS genetic variations are likely involved in modulating the magnitude and quality of the adaptive immune responses to live attenuated rubella vaccine.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Haplotype block structure of the OAS1 gene region in the study cohort. The LD block structure was analyzed using Haploview software, version 3.32. SNPs in the OAS1 region clustered into two blocks of linkage disequilibrium. The location of the splicing variant rs10774671 (boxed; not genotyped but in one bin/tight LD with rs1051042 and rs2660) is shown. The r2 color scheme is white (r2 = 0), shades of gray (0 < r2 < 1), black (r2 = 1).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Dean M., Carrington M., O'Brien S.J. Balanced polymorphism selected by genetic versus infectious human disease. Annu Rev Genomics Hum Genet. 2002;3:263–292. - PubMed
    1. Hill A.V. The genomics and genetics of human infectious disease susceptibility. Annu Rev Genomics Hum Genet. 2001;2:373–400. - PubMed
    1. Hill A.V. Aspects of genetic susceptibility to human infectious diseases. Annu Rev Genet. 2006;40:469–486. - PubMed
    1. Poland G.A., Ovsyannikova I.G., Jacobson R.M., Smith D.I. Heterogeneity in vaccine immune response: The role of immunogenetics and the emerging field of vaccinomics. Clin Pharmacol Ther. 2007;82:653–664. - PubMed
    1. Dhiman N., Ovsyannikova I.G., Vierkant R.A., Ryan J.E., Pankratz V.S., Jacobson R.M. Associations between SNPs in toll-like receptors and related intracellular signaling molecules and immune responses to measles vaccine: Preliminary results. Vaccine. 2008;26:1731–1736. - PMC - PubMed

Publication types

MeSH terms