Associations between single nucleotide polymorphisms and haplotypes in cytokine and cytokine receptor genes and immunity to measles vaccination

Iana H. Haralambieva; Inna G. Ovsyannikova; Richard B. Kennedy; Robert A. Vierkant; V. Shane Pankratz; Robert M. Jacobson; Gregory A. Poland

doi:10.1016/j.vaccine.2011.08.083

Associations between single nucleotide polymorphisms and haplotypes in cytokine and cytokine receptor genes and immunity to measles vaccination

Iana H. Haralambieva, Inna G. Ovsyannikova, Richard B. Kennedy, Robert A. Vierkant, V. Shane Pankratz, Robert M. Jacobson, Gregory A. Poland

Research output: Contribution to journal › Article › peer-review

50 Scopus citations

Abstract

Identification of host genetic determinants of measles vaccine-induced immunity can be used to design better vaccines and ultimately predict immune responses to vaccination.We performed a comprehensive candidate gene association study across 801 genetic markers in 56 cytokine/cytokine receptor genes, in a racially diverse cohort of 745 schoolchildren after two doses of MMR vaccine. Using linear regression methodologies we examined associations between SNPs/haplotypes and measles virus-specific immunity.Forty-eight significant SNP associations with variations in neutralizing antibodies and measles-specific IFNγ Elispot responses were identified (p<. 0.05). Our study replicated an important previously found association of a functional IL12B genetic variant rs3212227 with variations in measles-specific humoral immunity (p= 0.037). Similarly, two previously reported promoter IL10 and IL2 polymorphisms (rs1800890 and rs2069762) demonstrated associations with measles-specific cellular immunity in Caucasians (p≤. 0.034). Multiple IL7R polymorphisms, including a non-synonymous functional SNP (rs6897932/Thr244Ile), were associated with humoral (p≤. 0.024) and/or cellular (IFNγ Elispot, p≤. 0.023) measles-specific immune responses in Caucasians, but not African-Americans. Haplotype level analysis confirmed the association of IL7R genetic variants with measles vaccine-induced immunity in the Caucasian group (global p-value = 0.003).Our results validate previous findings and identify new plausible genetic determinants, including IL7R polymorphisms, regulating measles vaccine-induced immunity in a race-specific manner.

Original language	English (US)
Pages (from-to)	7883-7895
Number of pages	13
Journal	Vaccine
Volume	29
Issue number	45
DOIs	https://doi.org/10.1016/j.vaccine.2011.08.083
State	Published - Oct 19 2011

Keywords

Cytokine
Cytokine receptor
Haplotypes
Immunity
Measles vaccine
Single nucleotide polymorphisms

ASJC Scopus subject areas

Molecular Medicine
General Immunology and Microbiology
General Veterinary
Public Health, Environmental and Occupational Health
Infectious Diseases

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10.1016/j.vaccine.2011.08.083

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@article{119329fb5bd04747ab0caf9bcfa88aa0,

title = "Associations between single nucleotide polymorphisms and haplotypes in cytokine and cytokine receptor genes and immunity to measles vaccination",

abstract = "Identification of host genetic determinants of measles vaccine-induced immunity can be used to design better vaccines and ultimately predict immune responses to vaccination.We performed a comprehensive candidate gene association study across 801 genetic markers in 56 cytokine/cytokine receptor genes, in a racially diverse cohort of 745 schoolchildren after two doses of MMR vaccine. Using linear regression methodologies we examined associations between SNPs/haplotypes and measles virus-specific immunity.Forty-eight significant SNP associations with variations in neutralizing antibodies and measles-specific IFNγ Elispot responses were identified (p<. 0.05). Our study replicated an important previously found association of a functional IL12B genetic variant rs3212227 with variations in measles-specific humoral immunity (p= 0.037). Similarly, two previously reported promoter IL10 and IL2 polymorphisms (rs1800890 and rs2069762) demonstrated associations with measles-specific cellular immunity in Caucasians (p≤. 0.034). Multiple IL7R polymorphisms, including a non-synonymous functional SNP (rs6897932/Thr244Ile), were associated with humoral (p≤. 0.024) and/or cellular (IFNγ Elispot, p≤. 0.023) measles-specific immune responses in Caucasians, but not African-Americans. Haplotype level analysis confirmed the association of IL7R genetic variants with measles vaccine-induced immunity in the Caucasian group (global p-value = 0.003).Our results validate previous findings and identify new plausible genetic determinants, including IL7R polymorphisms, regulating measles vaccine-induced immunity in a race-specific manner.",

keywords = "Cytokine, Cytokine receptor, Haplotypes, Immunity, Measles vaccine, Single nucleotide polymorphisms",

author = "Haralambieva, {Iana H.} and Ovsyannikova, {Inna G.} and Kennedy, {Richard B.} and Vierkant, {Robert A.} and Pankratz, {V. Shane} and Jacobson, {Robert M.} and Poland, {Gregory A.}",

note = "Funding Information: We thank the parents and children who participated in our study and the Mayo Vaccine Research Group nurses for subject recruitment. We thank the Mayo Vaccine Research Group laboratory personnel for technical help with the assays and Matthew J. Phan for assistance in preparing the manuscript. We thank Megan O{\textquoteright}Byrne for her contribution to statistical analyses. We thank David Rider and Ying Li for developing the SNP selection algorithm, and Julie M. Cunningham and the Mayo Advanced Genomic Technology Center for assistance with genotyping. The project described was supported by Award Numbers AI33144 and AI48793 (which recently received a MERIT Award) from the National Institute Of Allergy And Infectious Diseases , and 5UL1RR024150-03 from the National Center for Research Resources (NCRR) , a component of the National Institutes of Health, and the NIH Roadmap for Medical Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. ",

year = "2011",

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day = "19",

doi = "10.1016/j.vaccine.2011.08.083",

language = "English (US)",

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AU - Haralambieva, Iana H.

AU - Ovsyannikova, Inna G.

AU - Kennedy, Richard B.

AU - Vierkant, Robert A.

AU - Pankratz, V. Shane

AU - Jacobson, Robert M.

AU - Poland, Gregory A.

N1 - Funding Information: We thank the parents and children who participated in our study and the Mayo Vaccine Research Group nurses for subject recruitment. We thank the Mayo Vaccine Research Group laboratory personnel for technical help with the assays and Matthew J. Phan for assistance in preparing the manuscript. We thank Megan O’Byrne for her contribution to statistical analyses. We thank David Rider and Ying Li for developing the SNP selection algorithm, and Julie M. Cunningham and the Mayo Advanced Genomic Technology Center for assistance with genotyping. The project described was supported by Award Numbers AI33144 and AI48793 (which recently received a MERIT Award) from the National Institute Of Allergy And Infectious Diseases , and 5UL1RR024150-03 from the National Center for Research Resources (NCRR) , a component of the National Institutes of Health, and the NIH Roadmap for Medical Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health.

PY - 2011/10/19

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N2 - Identification of host genetic determinants of measles vaccine-induced immunity can be used to design better vaccines and ultimately predict immune responses to vaccination.We performed a comprehensive candidate gene association study across 801 genetic markers in 56 cytokine/cytokine receptor genes, in a racially diverse cohort of 745 schoolchildren after two doses of MMR vaccine. Using linear regression methodologies we examined associations between SNPs/haplotypes and measles virus-specific immunity.Forty-eight significant SNP associations with variations in neutralizing antibodies and measles-specific IFNγ Elispot responses were identified (p<. 0.05). Our study replicated an important previously found association of a functional IL12B genetic variant rs3212227 with variations in measles-specific humoral immunity (p= 0.037). Similarly, two previously reported promoter IL10 and IL2 polymorphisms (rs1800890 and rs2069762) demonstrated associations with measles-specific cellular immunity in Caucasians (p≤. 0.034). Multiple IL7R polymorphisms, including a non-synonymous functional SNP (rs6897932/Thr244Ile), were associated with humoral (p≤. 0.024) and/or cellular (IFNγ Elispot, p≤. 0.023) measles-specific immune responses in Caucasians, but not African-Americans. Haplotype level analysis confirmed the association of IL7R genetic variants with measles vaccine-induced immunity in the Caucasian group (global p-value = 0.003).Our results validate previous findings and identify new plausible genetic determinants, including IL7R polymorphisms, regulating measles vaccine-induced immunity in a race-specific manner.

AB - Identification of host genetic determinants of measles vaccine-induced immunity can be used to design better vaccines and ultimately predict immune responses to vaccination.We performed a comprehensive candidate gene association study across 801 genetic markers in 56 cytokine/cytokine receptor genes, in a racially diverse cohort of 745 schoolchildren after two doses of MMR vaccine. Using linear regression methodologies we examined associations between SNPs/haplotypes and measles virus-specific immunity.Forty-eight significant SNP associations with variations in neutralizing antibodies and measles-specific IFNγ Elispot responses were identified (p<. 0.05). Our study replicated an important previously found association of a functional IL12B genetic variant rs3212227 with variations in measles-specific humoral immunity (p= 0.037). Similarly, two previously reported promoter IL10 and IL2 polymorphisms (rs1800890 and rs2069762) demonstrated associations with measles-specific cellular immunity in Caucasians (p≤. 0.034). Multiple IL7R polymorphisms, including a non-synonymous functional SNP (rs6897932/Thr244Ile), were associated with humoral (p≤. 0.024) and/or cellular (IFNγ Elispot, p≤. 0.023) measles-specific immune responses in Caucasians, but not African-Americans. Haplotype level analysis confirmed the association of IL7R genetic variants with measles vaccine-induced immunity in the Caucasian group (global p-value = 0.003).Our results validate previous findings and identify new plausible genetic determinants, including IL7R polymorphisms, regulating measles vaccine-induced immunity in a race-specific manner.

KW - Cytokine

KW - Cytokine receptor

KW - Haplotypes

KW - Immunity

KW - Measles vaccine

KW - Single nucleotide polymorphisms

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JO - Vaccine

JF - Vaccine

IS - 45

ER -

Associations between single nucleotide polymorphisms and haplotypes in cytokine and cytokine receptor genes and immunity to measles vaccination

Abstract

Keywords

ASJC Scopus subject areas

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