SNP/haplotype associations in cytokine and cytokine receptor genes and immunity to rubella vaccine
An effective immune response to vaccination is, in part, a complex interaction of alleles of multiple genes regulating cytokine networks. We conducted a genotyping study of Th1/Th2/inflammatory cytokines/cytokine receptors in healthy children (n = 738, 11-19 years) to determine associations between...
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| Veröffentlicht in: | Immunogenetics (New York) 2010-04, Vol.62 (4), p.197-210 |
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| creator | Dhiman, Neelam Haralambieva, Iana H Kennedy, Richard B Vierkant, Robert A O'Byrne, Megan M Ovsyannikova, Inna G Jacobson, Robert M Poland, Gregory A |
| description | An effective immune response to vaccination is, in part, a complex interaction of alleles of multiple genes regulating cytokine networks. We conducted a genotyping study of Th1/Th2/inflammatory cytokines/cytokine receptors in healthy children (n = 738, 11-19 years) to determine associations between individual single-nucleotide polymorphisms (SNPs)/haplotypes and immune outcomes after two doses of rubella vaccine. SNPs (n = 501) were selected using the ldSelect-approach and genotyped using Illumina GoldenGate™ and TaqMan assays. Rubella-IgG levels were measured by immunoassay and secreted cytokines by ELISA. Linear regression and post hoc haplotype analyses were used to determine associations between single SNPs/haplotypes and immune outcomes. Increased carriage of minor alleles for the promoter SNPs (rs2844482 and rs2857708) of the TNFA gene were associated with dose-related increases in rubella antibodies. IL-6 secretion was co-directionally associated (p ≤ 0.01) with five intronic SNPs in the TNFRSF1B gene in an allele dose-related manner, while five promoter/intronic SNPs in the IL12B gene were associated with variations in IL-6 secretion. TNFA haplotype AAACGGGGC (t-statistic = 3.32) and IL12B promoter haplotype TAG (t-statistic = 2.66) were associated with higher levels of (p ≤ 0.01) rubella-IgG and IL-6 secretion, respectively. We identified individual SNPs/haplotypes in TNFA/TNFRSF1B and IL12B genes that appear to modulate immunity to rubella vaccination. Identification of such “genetic fingerprints” may predict the outcome of vaccine response and inform new vaccine strategies. |
| doi_str_mv | 10.1007/s00251-010-0423-6 |
| format | Article |
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We conducted a genotyping study of Th1/Th2/inflammatory cytokines/cytokine receptors in healthy children (n = 738, 11-19 years) to determine associations between individual single-nucleotide polymorphisms (SNPs)/haplotypes and immune outcomes after two doses of rubella vaccine. SNPs (n = 501) were selected using the ldSelect-approach and genotyped using Illumina GoldenGate™ and TaqMan assays. Rubella-IgG levels were measured by immunoassay and secreted cytokines by ELISA. Linear regression and post hoc haplotype analyses were used to determine associations between single SNPs/haplotypes and immune outcomes. Increased carriage of minor alleles for the promoter SNPs (rs2844482 and rs2857708) of the TNFA gene were associated with dose-related increases in rubella antibodies. IL-6 secretion was co-directionally associated (p ≤ 0.01) with five intronic SNPs in the TNFRSF1B gene in an allele dose-related manner, while five promoter/intronic SNPs in the IL12B gene were associated with variations in IL-6 secretion. TNFA haplotype AAACGGGGC (t-statistic = 3.32) and IL12B promoter haplotype TAG (t-statistic = 2.66) were associated with higher levels of (p ≤ 0.01) rubella-IgG and IL-6 secretion, respectively. We identified individual SNPs/haplotypes in TNFA/TNFRSF1B and IL12B genes that appear to modulate immunity to rubella vaccination. Identification of such “genetic fingerprints” may predict the outcome of vaccine response and inform new vaccine strategies.</description><identifier>ISSN: 0093-7711</identifier><identifier>EISSN: 1432-1211</identifier><identifier>DOI: 10.1007/s00251-010-0423-6</identifier><identifier>PMID: 20217072</identifier><language>eng</language><publisher>Berlin/Heidelberg: Berlin/Heidelberg : Springer-Verlag</publisher><subject>Adolescent ; Adult ; Allergology ; Antibodies ; Antibodies, Viral - blood ; Biomedical and Life Sciences ; Biomedicine ; Cell Biology ; Child ; Cytokines ; Cytokines - genetics ; Female ; Gene Function ; Genes ; Haplotypes ; Human Genetics ; Humans ; Immune response ; Immunity, Cellular ; Immunoassay ; Immunoglobulin G - blood ; Immunology ; Interleukin-6 - genetics ; Interleukin-6 - immunology ; Male ; Original Paper ; Polymorphism, Single Nucleotide - genetics ; Promoter Regions, Genetic ; Proteins ; Receptors, Cytokine - genetics ; Rubella ; Rubella - genetics ; Rubella - immunology ; Rubella Vaccine - immunology ; Tumor Necrosis Factor-alpha - genetics ; Tumor Necrosis Factor-alpha - immunology ; Vaccination ; Vaccines ; Young Adult</subject><ispartof>Immunogenetics (New York), 2010-04, Vol.62 (4), p.197-210</ispartof><rights>Mayo Clinic 2010</rights><rights>Springer-Verlag 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c492t-9bcd2e6d6a83ccdee304b9133aff788cc6e979c7dacb1cc03a36a4ab90c97f9a3</citedby><cites>FETCH-LOGICAL-c492t-9bcd2e6d6a83ccdee304b9133aff788cc6e979c7dacb1cc03a36a4ab90c97f9a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00251-010-0423-6$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00251-010-0423-6$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20217072$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dhiman, Neelam</creatorcontrib><creatorcontrib>Haralambieva, Iana H</creatorcontrib><creatorcontrib>Kennedy, Richard B</creatorcontrib><creatorcontrib>Vierkant, Robert A</creatorcontrib><creatorcontrib>O'Byrne, Megan M</creatorcontrib><creatorcontrib>Ovsyannikova, Inna G</creatorcontrib><creatorcontrib>Jacobson, Robert M</creatorcontrib><creatorcontrib>Poland, Gregory A</creatorcontrib><title>SNP/haplotype associations in cytokine and cytokine receptor genes and immunity to rubella vaccine</title><title>Immunogenetics (New York)</title><addtitle>Immunogenetics</addtitle><addtitle>Immunogenetics</addtitle><description>An effective immune response to vaccination is, in part, a complex interaction of alleles of multiple genes regulating cytokine networks. We conducted a genotyping study of Th1/Th2/inflammatory cytokines/cytokine receptors in healthy children (n = 738, 11-19 years) to determine associations between individual single-nucleotide polymorphisms (SNPs)/haplotypes and immune outcomes after two doses of rubella vaccine. SNPs (n = 501) were selected using the ldSelect-approach and genotyped using Illumina GoldenGate™ and TaqMan assays. Rubella-IgG levels were measured by immunoassay and secreted cytokines by ELISA. Linear regression and post hoc haplotype analyses were used to determine associations between single SNPs/haplotypes and immune outcomes. Increased carriage of minor alleles for the promoter SNPs (rs2844482 and rs2857708) of the TNFA gene were associated with dose-related increases in rubella antibodies. IL-6 secretion was co-directionally associated (p ≤ 0.01) with five intronic SNPs in the TNFRSF1B gene in an allele dose-related manner, while five promoter/intronic SNPs in the IL12B gene were associated with variations in IL-6 secretion. TNFA haplotype AAACGGGGC (t-statistic = 3.32) and IL12B promoter haplotype TAG (t-statistic = 2.66) were associated with higher levels of (p ≤ 0.01) rubella-IgG and IL-6 secretion, respectively. We identified individual SNPs/haplotypes in TNFA/TNFRSF1B and IL12B genes that appear to modulate immunity to rubella vaccination. Identification of such “genetic fingerprints” may predict the outcome of vaccine response and inform new vaccine strategies.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Allergology</subject><subject>Antibodies</subject><subject>Antibodies, Viral - blood</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cell Biology</subject><subject>Child</subject><subject>Cytokines</subject><subject>Cytokines - genetics</subject><subject>Female</subject><subject>Gene Function</subject><subject>Genes</subject><subject>Haplotypes</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immunity, Cellular</subject><subject>Immunoassay</subject><subject>Immunoglobulin G - blood</subject><subject>Immunology</subject><subject>Interleukin-6 - genetics</subject><subject>Interleukin-6 - immunology</subject><subject>Male</subject><subject>Original Paper</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Promoter Regions, Genetic</subject><subject>Proteins</subject><subject>Receptors, Cytokine - genetics</subject><subject>Rubella</subject><subject>Rubella - genetics</subject><subject>Rubella - immunology</subject><subject>Rubella Vaccine - immunology</subject><subject>Tumor Necrosis Factor-alpha - genetics</subject><subject>Tumor Necrosis Factor-alpha - immunology</subject><subject>Vaccination</subject><subject>Vaccines</subject><subject>Young Adult</subject><issn>0093-7711</issn><issn>1432-1211</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kc1u1TAQhS0EoreFB2ADEZuuQmfsNI43SFXFn1QBUunacibOrUtiBzupdN8eX1JaYMFqZJ1vzvjoMPYC4Q0CyJMEwE-xBIQSKi7K-hHbYCV4iRzxMdsAKFFKiXjADlO6AcBTxeun7IADRwmSb1h7-fnrybWZhjDvJluYlAI5M7vgU-F8Qbs5fHc-C757eERLdppDLLbW2_RLc-O4eDfvijkUcWntMJji1hBl_Bl70psh2ed384hdvX_37fxjefHlw6fzs4uSKsXnUrXUcVt3tWkEUWetgKpVKITpe9k0RLVVUpHsDLVIBMKI2lSmVUBK9sqII_Z29Z2WdrQdWT9HM-gputHEnQ7G6b8V7671Ntxq3tQCFM8Gx3cGMfxYbJr16BLto3gblqSlEKISUtWZfP0PeROW6HM6zXMzChU2GcIVohhSira__wqC3ven1_507k_v-9N745d_Zrjf-F1YBvgKpCz5rY0Pl__n-mpd6k3QZhtd0leXHFAANtk5B_oJYpKx4A</recordid><startdate>20100401</startdate><enddate>20100401</enddate><creator>Dhiman, Neelam</creator><creator>Haralambieva, Iana H</creator><creator>Kennedy, Richard B</creator><creator>Vierkant, Robert A</creator><creator>O'Byrne, Megan M</creator><creator>Ovsyannikova, Inna G</creator><creator>Jacobson, Robert M</creator><creator>Poland, Gregory A</creator><general>Berlin/Heidelberg : Springer-Verlag</general><general>Springer-Verlag</general><general>Springer Nature B.V</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20100401</creationdate><title>SNP/haplotype associations in cytokine and cytokine receptor genes and immunity to rubella vaccine</title><author>Dhiman, Neelam ; Haralambieva, Iana H ; Kennedy, Richard B ; Vierkant, Robert A ; O'Byrne, Megan M ; Ovsyannikova, Inna G ; Jacobson, Robert M ; Poland, Gregory A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c492t-9bcd2e6d6a83ccdee304b9133aff788cc6e979c7dacb1cc03a36a4ab90c97f9a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Allergology</topic><topic>Antibodies</topic><topic>Antibodies, Viral - 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We conducted a genotyping study of Th1/Th2/inflammatory cytokines/cytokine receptors in healthy children (n = 738, 11-19 years) to determine associations between individual single-nucleotide polymorphisms (SNPs)/haplotypes and immune outcomes after two doses of rubella vaccine. SNPs (n = 501) were selected using the ldSelect-approach and genotyped using Illumina GoldenGate™ and TaqMan assays. Rubella-IgG levels were measured by immunoassay and secreted cytokines by ELISA. Linear regression and post hoc haplotype analyses were used to determine associations between single SNPs/haplotypes and immune outcomes. Increased carriage of minor alleles for the promoter SNPs (rs2844482 and rs2857708) of the TNFA gene were associated with dose-related increases in rubella antibodies. IL-6 secretion was co-directionally associated (p ≤ 0.01) with five intronic SNPs in the TNFRSF1B gene in an allele dose-related manner, while five promoter/intronic SNPs in the IL12B gene were associated with variations in IL-6 secretion. TNFA haplotype AAACGGGGC (t-statistic = 3.32) and IL12B promoter haplotype TAG (t-statistic = 2.66) were associated with higher levels of (p ≤ 0.01) rubella-IgG and IL-6 secretion, respectively. We identified individual SNPs/haplotypes in TNFA/TNFRSF1B and IL12B genes that appear to modulate immunity to rubella vaccination. Identification of such “genetic fingerprints” may predict the outcome of vaccine response and inform new vaccine strategies.</abstract><cop>Berlin/Heidelberg</cop><pub>Berlin/Heidelberg : Springer-Verlag</pub><pmid>20217072</pmid><doi>10.1007/s00251-010-0423-6</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Adult Allergology Antibodies Antibodies, Viral - blood Biomedical and Life Sciences Biomedicine Cell Biology Child Cytokines Cytokines - genetics Female Gene Function Genes Haplotypes Human Genetics Humans Immune response Immunity, Cellular Immunoassay Immunoglobulin G - blood Immunology Interleukin-6 - genetics Interleukin-6 - immunology Male Original Paper Polymorphism, Single Nucleotide - genetics Promoter Regions, Genetic Proteins Receptors, Cytokine - genetics Rubella Rubella - genetics Rubella - immunology Rubella Vaccine - immunology Tumor Necrosis Factor-alpha - genetics Tumor Necrosis Factor-alpha - immunology Vaccination Vaccines Young Adult |
| title | SNP/haplotype associations in cytokine and cytokine receptor genes and immunity to rubella vaccine |
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