Replication of associations between cytokine and cytokine receptor single nucleotide polymorphisms and measles-specific adaptive immunophenotypic extremes

Sarah J. White; Iana H. Haralambieva; Inna G. Ovsyannikova; Robert A. Vierkant; Megan M. O'Byrne; Gregory A. Poland

doi:10.1016/j.humimm.2012.03.015

Replication of associations between cytokine and cytokine receptor single nucleotide polymorphisms and measles-specific adaptive immunophenotypic extremes

Sarah J. White, Iana H. Haralambieva, Inna G. Ovsyannikova, Robert A. Vierkant, Megan M. O'Byrne, Gregory A. Poland

General Internal Medicine

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

10 Scopus citations

Abstract

Our objective was to replicate previously reported associations between cytokine and cytokine receptor SNPs and humoral and CMI (cell-mediated immune) responses to measles vaccine. All subjects (n=758) received two doses of MMR (measles/mumps/rubella) vaccine. From these subjects, candidate cytokine and cytokine receptor SNPs were genotyped and analyzed in 29-30 subjects falling into one of four "extreme" humoral (Ab^high/low) and CMI (CMI^high/low) response quadrants. Associations between seven SNPs (out of 11 in the discovery study) and measles-specific neutralizing antibody levels and IFN-γ ELISPOT responses were evaluated using chi-square tests. We found one replicated association for SNP rs372889 in the IL12RB1 gene (P=0.03 for Ab^highCMI^high vs. Ab^lowCMI^low). Our findings demonstrate the importance of replicating genotypic-phenotypic associations, which can be achieved using immunophenotypic extremes and smaller sample sizes. We speculate that IL12RB1 polymorphisms may affect IL-12 and IL-23 binding and downstream effects, which are critical cytokines in the CMI response to measles vaccine.

Original language	English (US)
Pages (from-to)	636-640
Number of pages	5
Journal	Human Immunology
Volume	73
Issue number	6
DOIs	https://doi.org/10.1016/j.humimm.2012.03.015
State	Published - Jun 2012

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1016/j.humimm.2012.03.015

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title = "Replication of associations between cytokine and cytokine receptor single nucleotide polymorphisms and measles-specific adaptive immunophenotypic extremes",

abstract = "Our objective was to replicate previously reported associations between cytokine and cytokine receptor SNPs and humoral and CMI (cell-mediated immune) responses to measles vaccine. All subjects (n=758) received two doses of MMR (measles/mumps/rubella) vaccine. From these subjects, candidate cytokine and cytokine receptor SNPs were genotyped and analyzed in 29-30 subjects falling into one of four {"}extreme{"} humoral (Abhigh/low) and CMI (CMIhigh/low) response quadrants. Associations between seven SNPs (out of 11 in the discovery study) and measles-specific neutralizing antibody levels and IFN-γ ELISPOT responses were evaluated using chi-square tests. We found one replicated association for SNP rs372889 in the IL12RB1 gene (P=0.03 for AbhighCMIhigh vs. AblowCMIlow). Our findings demonstrate the importance of replicating genotypic-phenotypic associations, which can be achieved using immunophenotypic extremes and smaller sample sizes. We speculate that IL12RB1 polymorphisms may affect IL-12 and IL-23 binding and downstream effects, which are critical cytokines in the CMI response to measles vaccine.",

author = "White, {Sarah J.} and Haralambieva, {Iana H.} and Ovsyannikova, {Inna G.} and Vierkant, {Robert A.} and O'Byrne, {Megan M.} and Poland, {Gregory A.}",

note = "Funding Information: We thank the parents and their children as well as the young adults who participated in our study and the Mayo Vaccine Research Group nurses for subject recruitment. We thank Dr. Neelam Dhiman and Dr. V. Shane Pankratz for their work on the discovery study. We thank the Mayo Vaccine Research Group laboratory personnel for technical help with the assays, especially Benjamin Umlauf, Eric Swanson and Norman Pinsky. We thank David Rider and Ying Li for developing the SNP selection algorithm and Dr. Julie Cunningham and the Mayo Advanced Genomic Technology Center for assistance with genotyping. This work was supported by National Institute of Health grants R01 AI33144-15 and R01 AI48973-11, and 1 UL1 RR024150-01 from the National Center for Research Resources, a component of the National Institutes of Health, and the National Institute of Health Roadmap for Medical Research. ",

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language = "English (US)",

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T1 - Replication of associations between cytokine and cytokine receptor single nucleotide polymorphisms and measles-specific adaptive immunophenotypic extremes

AU - White, Sarah J.

AU - Haralambieva, Iana H.

AU - Ovsyannikova, Inna G.

AU - Vierkant, Robert A.

AU - O'Byrne, Megan M.

AU - Poland, Gregory A.

N1 - Funding Information: We thank the parents and their children as well as the young adults who participated in our study and the Mayo Vaccine Research Group nurses for subject recruitment. We thank Dr. Neelam Dhiman and Dr. V. Shane Pankratz for their work on the discovery study. We thank the Mayo Vaccine Research Group laboratory personnel for technical help with the assays, especially Benjamin Umlauf, Eric Swanson and Norman Pinsky. We thank David Rider and Ying Li for developing the SNP selection algorithm and Dr. Julie Cunningham and the Mayo Advanced Genomic Technology Center for assistance with genotyping. This work was supported by National Institute of Health grants R01 AI33144-15 and R01 AI48973-11, and 1 UL1 RR024150-01 from the National Center for Research Resources, a component of the National Institutes of Health, and the National Institute of Health Roadmap for Medical Research.

PY - 2012/6

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N2 - Our objective was to replicate previously reported associations between cytokine and cytokine receptor SNPs and humoral and CMI (cell-mediated immune) responses to measles vaccine. All subjects (n=758) received two doses of MMR (measles/mumps/rubella) vaccine. From these subjects, candidate cytokine and cytokine receptor SNPs were genotyped and analyzed in 29-30 subjects falling into one of four "extreme" humoral (Abhigh/low) and CMI (CMIhigh/low) response quadrants. Associations between seven SNPs (out of 11 in the discovery study) and measles-specific neutralizing antibody levels and IFN-γ ELISPOT responses were evaluated using chi-square tests. We found one replicated association for SNP rs372889 in the IL12RB1 gene (P=0.03 for AbhighCMIhigh vs. AblowCMIlow). Our findings demonstrate the importance of replicating genotypic-phenotypic associations, which can be achieved using immunophenotypic extremes and smaller sample sizes. We speculate that IL12RB1 polymorphisms may affect IL-12 and IL-23 binding and downstream effects, which are critical cytokines in the CMI response to measles vaccine.

AB - Our objective was to replicate previously reported associations between cytokine and cytokine receptor SNPs and humoral and CMI (cell-mediated immune) responses to measles vaccine. All subjects (n=758) received two doses of MMR (measles/mumps/rubella) vaccine. From these subjects, candidate cytokine and cytokine receptor SNPs were genotyped and analyzed in 29-30 subjects falling into one of four "extreme" humoral (Abhigh/low) and CMI (CMIhigh/low) response quadrants. Associations between seven SNPs (out of 11 in the discovery study) and measles-specific neutralizing antibody levels and IFN-γ ELISPOT responses were evaluated using chi-square tests. We found one replicated association for SNP rs372889 in the IL12RB1 gene (P=0.03 for AbhighCMIhigh vs. AblowCMIlow). Our findings demonstrate the importance of replicating genotypic-phenotypic associations, which can be achieved using immunophenotypic extremes and smaller sample sizes. We speculate that IL12RB1 polymorphisms may affect IL-12 and IL-23 binding and downstream effects, which are critical cytokines in the CMI response to measles vaccine.

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ER -

Replication of associations between cytokine and cytokine receptor single nucleotide polymorphisms and measles-specific adaptive immunophenotypic extremes

Abstract

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