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

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 cohor...

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Autores principales: Haralambieva, Iana H., Dhiman, Neelam, Ovsyannikova, Inna G., Vierkant, Robert A., Pankratz, V. Shane, Jacobson, Robert M., Poland, Gregory A.
Formato: Texto
Lenguaje:English
Publicado: American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842477/
https://www.ncbi.nlm.nih.gov/pubmed/20079393
http://dx.doi.org/10.1016/j.humimm.2010.01.004
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author Haralambieva, Iana H.
Dhiman, Neelam
Ovsyannikova, Inna G.
Vierkant, Robert A.
Pankratz, V. Shane
Jacobson, Robert M.
Poland, Gregory A.
author_facet Haralambieva, Iana H.
Dhiman, Neelam
Ovsyannikova, Inna G.
Vierkant, Robert A.
Pankratz, V. Shane
Jacobson, Robert M.
Poland, Gregory A.
author_sort Haralambieva, Iana H.
collection PubMed
description 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 ≤ 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 ≤ 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.
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spelling pubmed-28424772011-04-01 2′-5′-Oligoadenylate synthetase single-nucleotide polymorphisms and haplotypes are associated with variations in immune responses to rubella vaccine Haralambieva, Iana H. Dhiman, Neelam Ovsyannikova, Inna G. Vierkant, Robert A. Pankratz, V. Shane Jacobson, Robert M. Poland, Gregory A. Hum Immunol Article 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 ≤ 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 ≤ 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. American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. 2010-04 2010-01-31 /pmc/articles/PMC2842477/ /pubmed/20079393 http://dx.doi.org/10.1016/j.humimm.2010.01.004 Text en Copyright © 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Haralambieva, Iana H.
Dhiman, Neelam
Ovsyannikova, Inna G.
Vierkant, Robert A.
Pankratz, V. Shane
Jacobson, Robert M.
Poland, Gregory A.
2′-5′-Oligoadenylate synthetase single-nucleotide polymorphisms and haplotypes are associated with variations in immune responses to rubella vaccine
title 2′-5′-Oligoadenylate synthetase single-nucleotide polymorphisms and haplotypes are associated with variations in immune responses to rubella vaccine
title_full 2′-5′-Oligoadenylate synthetase single-nucleotide polymorphisms and haplotypes are associated with variations in immune responses to rubella vaccine
title_fullStr 2′-5′-Oligoadenylate synthetase single-nucleotide polymorphisms and haplotypes are associated with variations in immune responses to rubella vaccine
title_full_unstemmed 2′-5′-Oligoadenylate synthetase single-nucleotide polymorphisms and haplotypes are associated with variations in immune responses to rubella vaccine
title_short 2′-5′-Oligoadenylate synthetase single-nucleotide polymorphisms and haplotypes are associated with variations in immune responses to rubella vaccine
title_sort 2′-5′-oligoadenylate synthetase single-nucleotide polymorphisms and haplotypes are associated with variations in immune responses to rubella vaccine
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842477/
https://www.ncbi.nlm.nih.gov/pubmed/20079393
http://dx.doi.org/10.1016/j.humimm.2010.01.004
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