Impact of cytokine and cytokine receptor gene polymorphisms on cellular immunity after smallpox vaccination

被引:29
作者
Ovsyannikova, Inna G. [1 ,4 ]
Haralambieva, Iana H. [1 ,4 ]
Kennedy, Richard B. [1 ,4 ]
Pankratz, V. Shane [3 ]
Vierkant, Robert A. [3 ]
Jacobson, Robert M. [1 ,2 ]
Poland, Gregory A. [1 ,2 ,4 ]
机构
[1] Mayo Clin, Mayo Clin Vaccine Res Grp, Rochester, MN 55905 USA
[2] Mayo Clin, Dept Pediat & Adolescent Med, Rochester, MN 55905 USA
[3] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA
[4] Mayo Clin, Program Translat Immunovirol & Biodef, Rochester, MN 55905 USA
基金
美国国家卫生研究院;
关键词
Immunogenetics; SNPs; Smallpox vaccine; Cellular immunity; Caucasians; African-Americans; SINGLE-NUCLEOTIDE POLYMORPHISMS; ADVERSE EVENTS; ONLINE DATABASES; HUMAN-DISEASE; ANTIBODY-RESPONSE; ASSOCIATIONS; GENERATION; INFECTION; VIRULENCE; CELLS;
D O I
10.1016/j.gene.2012.08.021
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
We explored associations between SNPs in cytokine/cytokine receptor genes and cellular immunity in subjects following primary smallpox vaccination. We also analyzed the genotype-phenotype associations discovered in the Caucasian subjects among a cohort of African-Americans. In Caucasians we found 277 associations (p<0.05) between gene SNPs and inter-individual variations in IFN-alpha, IL-12p40, IL-1 beta, IL-2, and TNF-alpha secretion levels. A collection of SNPs in the IL1RN, IL2RB, IL4R, IL6, IL10RB, IL12A, and IL12RB2 genes had consistent associations among both Caucasians and African-Americans. A regulatory SNP (rs452204) in the El RN gene was significantly associated with higher levels of IL-2 secretion in an allele dose-dependent manner in both race groups (p = 0.05 for Caucasians and p = 0.002 for African-Americans). IL12RB2 polymorphism rs3790567 was associated with a dose-related decrease in IL-1 beta secretion (p = 0.009 for Caucasians and p = 0.01 for African-Americans). Our results demonstrate that variations in smallpox vaccine-induced cytokine responses are modulated by genetic polymorphisms in cytokine and cytokine receptor genes. (C) 2012 Elsevier B.V. All rights reserved.
引用
收藏
页码:59 / 65
页数:7
相关论文
共 34 条
[1]   Cytokine gene polymorphism in human disease: on-line databases [J].
Bidwell, J ;
Keen, L ;
Gallagher, G ;
Kimberly, R ;
Huizinga, T ;
McDermott, MF ;
Oksenberg, J ;
McNicholl, J ;
Pociot, F ;
Hardt, C ;
D'Alfonso, S .
GENES AND IMMUNITY, 1999, 1 (01) :3-19
[2]   Cytokine gene polymorphism in human disease: on-line databases, Supplement 1 [J].
Bidwell, J ;
Keen, L ;
Gallagher, G ;
Kimberly, R ;
Huizinga, T ;
McDermott, MF ;
Oksenberg, J ;
McNicholl, J ;
Pociot, F ;
Hardt, C ;
D'Alfonso, S .
GENES AND IMMUNITY, 2001, 2 (02) :61-70
[3]   CYTOKINES IN THE GENERATION OF IMMUNE-RESPONSES TO, AND RESOLUTION OF, VIRUS-INFECTION [J].
BIRON, CA .
CURRENT OPINION IN IMMUNOLOGY, 1994, 6 (04) :530-538
[4]   Genetic predisposition for adverse events after vaccination [J].
Crowe, James E., Jr. .
JOURNAL OF INFECTIOUS DISEASES, 2007, 196 (02) :176-177
[5]   Surfing a genetic association interaction network to identify modulators of antibody response to smallpox vaccine [J].
Davis, N. A. ;
Crowe, J. E., Jr. ;
Pajewski, N. M. ;
McKinney, B. A. .
GENES AND IMMUNITY, 2010, 11 (08) :630-636
[6]   Integrating genomics across drug discovery and development [J].
Debouck, Christine .
TOXICOLOGY LETTERS, 2009, 186 (01) :9-12
[7]   Associations between measles vaccine immunity and single-nucleotide polymorphisms in cytokine and cytokine receptor genes [J].
Dhiman, Neelam ;
Ovsyannikova, Inna G. ;
Cunningham, Julie M. ;
Vierkant, Robert A. ;
Kennedy, Richard B. ;
Pankratz, V. Shane ;
Poland, Gregory A. ;
Jacobson, Robert M. .
JOURNAL OF INFECTIOUS DISEASES, 2007, 195 (01) :21-29
[8]   Infection, fever, and exogenous and endogenous pyrogens: some concepts have changed [J].
Dinarello, CA .
JOURNAL OF ENDOTOXIN RESEARCH, 2004, 10 (04) :201-222
[9]   Variola virus immune evasion proteins [J].
Dunlop, LR ;
Oehlberg, KA ;
Reid, JJ ;
Avci, D ;
Rosengard, AM .
MICROBES AND INFECTION, 2003, 5 (11) :1049-1056
[10]   A novel polymorphism in the 5′ promoter region of the human interleukin-4 receptor α-chain gene is associated with decreased soluble interleukin-4 receptor protein levels [J].
Hackstein, H ;
Hecker, M ;
Kruse, S ;
Bohnert, A ;
Ober, C ;
Deichmann, KA ;
Bein, G .
IMMUNOGENETICS, 2001, 53 (04) :264-269