Genetic variation in the serotonin receptor gene affects immune responses in rheumatoid arthritis
Many genetic variants associate with the risk of developing rheumatoid arthritis (RA); however, their functional roles are largely unknown. Here, we aimed to investigate whether the RA-associated serotonin receptor 2A ( HTR2A) haplotype affects T-cell and monocyte functions. Patients with establishe...
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| Veröffentlicht in: | Genes and immunity 2013-03, Vol.14 (2), p.83-89 |
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| creator | Snir, O Hesselberg, E Amoudruz, P Klareskog, L Zarea-Ganji, I Catrina, A I Padyukov, L Malmström, V Seddighzadeh, M |
| description | Many genetic variants associate with the risk of developing rheumatoid arthritis (RA); however, their functional roles are largely unknown. Here, we aimed to investigate whether the RA-associated serotonin receptor 2A (
HTR2A)
haplotype affects T-cell and monocyte functions. Patients with established RA (
n
=379) were genotyped for two single-nucleotide polymorphisms (SNPs) in the
HTR2A
locus, rs6314 and rs1328674, to define presence of the risk haplotype for each individual. Patients with and without the RA-associated TC haplotype were selected and T-cell and monocyte function was monitored following
in vitro
stimulations with staphylococcal enterotoxin B and lipopolysaccharide (LPS) using multiparameter flow cytometry. Within the cohort, 44 patients were heterozygous for the TC haplotype (11.6%) while none were homozygous. Upon stimulation, T cells from TC-carrier patients produced more proinflammatory cytokines (tumor necrosis factor alpha (TNF-α), interleukin-17 (IL-17) and interferon gamma (IFN-γ)) and monocytes produced higher levels of TNF-α compared with patients carrying the non-TC haplotype (
P |
| doi_str_mv | 10.1038/gene.2012.56 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_swepu</sourceid><recordid>TN_cdi_swepub_primary_oai_swepub_ki_se_532636</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A322563675</galeid><sourcerecordid>A322563675</sourcerecordid><originalsourceid>FETCH-LOGICAL-c672t-54343cc557a6a6b672d0d0009b0860c735264cf9d55085ae245a1410ceb4bd913</originalsourceid><addsrcrecordid>eNqNkl1rFDEUhgdRbK3eeS0D3ii4a74zuRFK0VooCH5ch2zmzG7qTDImmar_3gy7bXelguQiOSfP-yY5OVX1HKMlRrR5uwYPS4IwWXLxoDrGTIoFZxI9nNdCLFgj1VH1JKUrhLDAQj2ujgglnFEujytzXuTZ2fraRGeyC752vs4bqBPEkIMvUQQLYw6xno-qTdeBzal2wzCVMEIag0-QZl3cwDSYHFxbm5g30WWXnlaPOtMneLabT6pvH95_Pfu4uPx0fnF2ermwQpJcrkwZtZZzaYQRq5JrUYsQUivUCGQl5UQw26mWc9RwA4RxgxlGFlZs1SpMT6rF1jf9hHFa6TG6wcTfOhind6nvZQWaUyKoKLz6Jz_G0N6JboS46IiQvCnad1ttAQZoLfgcTX9ocbDj3Uavw7WmXFHckGLwamcQw48JUtaDSxb63ngIU9KYEtpgQRv5HyjmgjRcqoK-_Au9ClP0peozxRRWksk7am160M53oVzRzqb6lBLCS3EkL9TyHqqMFgZng4fOlfyB4PWBoDAZfuW1mVLSF18-H7JvtqyNIaUI3W3pMNJzV-u51fTc1ZrPX_Viv9y38E0b7_192fJriHsPv8_wDwI4Aeg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1314919747</pqid></control><display><type>article</type><title>Genetic variation in the serotonin receptor gene affects immune responses in rheumatoid arthritis</title><source>MEDLINE</source><source>SWEPUB Freely available online</source><source>Free E-Journal (出版社公開部分のみ）</source><source>Alma/SFX Local Collection</source><creator>Snir, O ; Hesselberg, E ; Amoudruz, P ; Klareskog, L ; Zarea-Ganji, I ; Catrina, A I ; Padyukov, L ; Malmström, V ; Seddighzadeh, M</creator><creatorcontrib>Snir, O ; Hesselberg, E ; Amoudruz, P ; Klareskog, L ; Zarea-Ganji, I ; Catrina, A I ; Padyukov, L ; Malmström, V ; Seddighzadeh, M</creatorcontrib><description>Many genetic variants associate with the risk of developing rheumatoid arthritis (RA); however, their functional roles are largely unknown. Here, we aimed to investigate whether the RA-associated serotonin receptor 2A (
HTR2A)
haplotype affects T-cell and monocyte functions. Patients with established RA (
n
=379) were genotyped for two single-nucleotide polymorphisms (SNPs) in the
HTR2A
locus, rs6314 and rs1328674, to define presence of the risk haplotype for each individual. Patients with and without the RA-associated TC haplotype were selected and T-cell and monocyte function was monitored following
in vitro
stimulations with staphylococcal enterotoxin B and lipopolysaccharide (LPS) using multiparameter flow cytometry. Within the cohort, 44 patients were heterozygous for the TC haplotype (11.6%) while none were homozygous. Upon stimulation, T cells from TC-carrier patients produced more proinflammatory cytokines (tumor necrosis factor alpha (TNF-α), interleukin-17 (IL-17) and interferon gamma (IFN-γ)) and monocytes produced higher levels of TNF-α compared with patients carrying the non-TC haplotype (
P
<0.05 and 0.01, respectively). Such cytokine production could be inhibited in the presence of the selective 5-HT2 receptor agonist (2,5-Dimethoxy-4-iodoamphetamine, DOI); interestingly, this effect was more pronounced in TC carriers. Our data demonstrate that association of RA with a distinct serotonin receptor haplotype has functional impact by affecting the immunological phenotype of T cells and monocytes.</description><identifier>ISSN: 1466-4879</identifier><identifier>ISSN: 1476-5470</identifier><identifier>EISSN: 1476-5470</identifier><identifier>DOI: 10.1038/gene.2012.56</identifier><identifier>PMID: 23254357</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/208/726/649 ; 631/250/248 ; 692/699/249/1313/498 ; Adult ; Aged ; Aged, 80 and over ; Amphetamines - pharmacology ; Arthritis, Rheumatoid - genetics ; Arthritis, Rheumatoid - immunology ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Cytokines ; Data processing ; Enterotoxins - immunology ; Flow cytometry ; gamma -Interferon ; Gene Expression ; Gene loci ; Genetic aspects ; Genetic diversity ; Genetic Variation ; Genomes ; Genotype ; Haplotypes ; Health aspects ; Human Genetics ; Humans ; Immune response ; Immunology ; Inflammation ; Interferon-gamma - metabolism ; Interleukin 17 ; Interleukin-17 - metabolism ; Lipopolysaccharides ; Lipopolysaccharides - immunology ; Lymphocytes ; Lymphocytes T ; Medicin och hälsovetenskap ; Middle Aged ; Monocytes ; Monocytes - immunology ; Original ; original-article ; Physiological aspects ; Physiology ; Polymorphism, Single Nucleotide ; Receptor, Serotonin, 5-HT2A - genetics ; Rheumatoid arthritis ; Rheumatology ; Serotonin ; Serotonin Receptor Agonists - pharmacology ; Serotonin receptors ; Serotonin S2 receptors ; Single-nucleotide polymorphism ; Smooth muscle ; Staphylococcal enterotoxin B ; T cells ; T-Lymphocytes - immunology ; Tumor necrosis factor- alpha ; Tumor Necrosis Factor-alpha - metabolism ; Tumor necrosis factor-TNF</subject><ispartof>Genes and immunity, 2013-03, Vol.14 (2), p.83-89</ispartof><rights>The Author(s) 2013</rights><rights>COPYRIGHT 2013 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Mar 2013</rights><rights>Copyright © 2013 Macmillan Publishers Limited 2013 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c672t-54343cc557a6a6b672d0d0009b0860c735264cf9d55085ae245a1410ceb4bd913</citedby><cites>FETCH-LOGICAL-c672t-54343cc557a6a6b672d0d0009b0860c735264cf9d55085ae245a1410ceb4bd913</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,552,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23254357$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:126326758$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Snir, O</creatorcontrib><creatorcontrib>Hesselberg, E</creatorcontrib><creatorcontrib>Amoudruz, P</creatorcontrib><creatorcontrib>Klareskog, L</creatorcontrib><creatorcontrib>Zarea-Ganji, I</creatorcontrib><creatorcontrib>Catrina, A I</creatorcontrib><creatorcontrib>Padyukov, L</creatorcontrib><creatorcontrib>Malmström, V</creatorcontrib><creatorcontrib>Seddighzadeh, M</creatorcontrib><title>Genetic variation in the serotonin receptor gene affects immune responses in rheumatoid arthritis</title><title>Genes and immunity</title><addtitle>Genes Immun</addtitle><addtitle>Genes Immun</addtitle><description>Many genetic variants associate with the risk of developing rheumatoid arthritis (RA); however, their functional roles are largely unknown. Here, we aimed to investigate whether the RA-associated serotonin receptor 2A (
HTR2A)
haplotype affects T-cell and monocyte functions. Patients with established RA (
n
=379) were genotyped for two single-nucleotide polymorphisms (SNPs) in the
HTR2A
locus, rs6314 and rs1328674, to define presence of the risk haplotype for each individual. Patients with and without the RA-associated TC haplotype were selected and T-cell and monocyte function was monitored following
in vitro
stimulations with staphylococcal enterotoxin B and lipopolysaccharide (LPS) using multiparameter flow cytometry. Within the cohort, 44 patients were heterozygous for the TC haplotype (11.6%) while none were homozygous. Upon stimulation, T cells from TC-carrier patients produced more proinflammatory cytokines (tumor necrosis factor alpha (TNF-α), interleukin-17 (IL-17) and interferon gamma (IFN-γ)) and monocytes produced higher levels of TNF-α compared with patients carrying the non-TC haplotype (
P
<0.05 and 0.01, respectively). Such cytokine production could be inhibited in the presence of the selective 5-HT2 receptor agonist (2,5-Dimethoxy-4-iodoamphetamine, DOI); interestingly, this effect was more pronounced in TC carriers. Our data demonstrate that association of RA with a distinct serotonin receptor haplotype has functional impact by affecting the immunological phenotype of T cells and monocytes.</description><subject>631/208/726/649</subject><subject>631/250/248</subject><subject>692/699/249/1313/498</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Amphetamines - pharmacology</subject><subject>Arthritis, Rheumatoid - genetics</subject><subject>Arthritis, Rheumatoid - immunology</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Cytokines</subject><subject>Data processing</subject><subject>Enterotoxins - immunology</subject><subject>Flow cytometry</subject><subject>gamma -Interferon</subject><subject>Gene Expression</subject><subject>Gene loci</subject><subject>Genetic aspects</subject><subject>Genetic diversity</subject><subject>Genetic Variation</subject><subject>Genomes</subject><subject>Genotype</subject><subject>Haplotypes</subject><subject>Health aspects</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immunology</subject><subject>Inflammation</subject><subject>Interferon-gamma - metabolism</subject><subject>Interleukin 17</subject><subject>Interleukin-17 - metabolism</subject><subject>Lipopolysaccharides</subject><subject>Lipopolysaccharides - immunology</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Medicin och hälsovetenskap</subject><subject>Middle Aged</subject><subject>Monocytes</subject><subject>Monocytes - immunology</subject><subject>Original</subject><subject>original-article</subject><subject>Physiological aspects</subject><subject>Physiology</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Receptor, Serotonin, 5-HT2A - genetics</subject><subject>Rheumatoid arthritis</subject><subject>Rheumatology</subject><subject>Serotonin</subject><subject>Serotonin Receptor Agonists - pharmacology</subject><subject>Serotonin receptors</subject><subject>Serotonin S2 receptors</subject><subject>Single-nucleotide polymorphism</subject><subject>Smooth muscle</subject><subject>Staphylococcal enterotoxin B</subject><subject>T cells</subject><subject>T-Lymphocytes - immunology</subject><subject>Tumor necrosis factor- alpha</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><subject>Tumor necrosis factor-TNF</subject><issn>1466-4879</issn><issn>1476-5470</issn><issn>1476-5470</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>D8T</sourceid><recordid>eNqNkl1rFDEUhgdRbK3eeS0D3ii4a74zuRFK0VooCH5ch2zmzG7qTDImmar_3gy7bXelguQiOSfP-yY5OVX1HKMlRrR5uwYPS4IwWXLxoDrGTIoFZxI9nNdCLFgj1VH1JKUrhLDAQj2ujgglnFEujytzXuTZ2fraRGeyC752vs4bqBPEkIMvUQQLYw6xno-qTdeBzal2wzCVMEIag0-QZl3cwDSYHFxbm5g30WWXnlaPOtMneLabT6pvH95_Pfu4uPx0fnF2ermwQpJcrkwZtZZzaYQRq5JrUYsQUivUCGQl5UQw26mWc9RwA4RxgxlGFlZs1SpMT6rF1jf9hHFa6TG6wcTfOhind6nvZQWaUyKoKLz6Jz_G0N6JboS46IiQvCnad1ttAQZoLfgcTX9ocbDj3Uavw7WmXFHckGLwamcQw48JUtaDSxb63ngIU9KYEtpgQRv5HyjmgjRcqoK-_Au9ClP0peozxRRWksk7am160M53oVzRzqb6lBLCS3EkL9TyHqqMFgZng4fOlfyB4PWBoDAZfuW1mVLSF18-H7JvtqyNIaUI3W3pMNJzV-u51fTc1ZrPX_Viv9y38E0b7_192fJriHsPv8_wDwI4Aeg</recordid><startdate>20130301</startdate><enddate>20130301</enddate><creator>Snir, O</creator><creator>Hesselberg, E</creator><creator>Amoudruz, P</creator><creator>Klareskog, L</creator><creator>Zarea-Ganji, I</creator><creator>Catrina, A I</creator><creator>Padyukov, L</creator><creator>Malmström, V</creator><creator>Seddighzadeh, M</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</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>ISR</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</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>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>20130301</creationdate><title>Genetic variation in the serotonin receptor gene affects immune responses in rheumatoid arthritis</title><author>Snir, O ; Hesselberg, E ; Amoudruz, P ; Klareskog, L ; Zarea-Ganji, I ; Catrina, A I ; Padyukov, L ; Malmström, V ; Seddighzadeh, M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c672t-54343cc557a6a6b672d0d0009b0860c735264cf9d55085ae245a1410ceb4bd913</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>631/208/726/649</topic><topic>631/250/248</topic><topic>692/699/249/1313/498</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Amphetamines - pharmacology</topic><topic>Arthritis, Rheumatoid - genetics</topic><topic>Arthritis, Rheumatoid - immunology</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Cytokines</topic><topic>Data processing</topic><topic>Enterotoxins - immunology</topic><topic>Flow cytometry</topic><topic>gamma -Interferon</topic><topic>Gene Expression</topic><topic>Gene loci</topic><topic>Genetic aspects</topic><topic>Genetic diversity</topic><topic>Genetic Variation</topic><topic>Genomes</topic><topic>Genotype</topic><topic>Haplotypes</topic><topic>Health aspects</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Immune response</topic><topic>Immunology</topic><topic>Inflammation</topic><topic>Interferon-gamma - metabolism</topic><topic>Interleukin 17</topic><topic>Interleukin-17 - metabolism</topic><topic>Lipopolysaccharides</topic><topic>Lipopolysaccharides - immunology</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Medicin och hälsovetenskap</topic><topic>Middle Aged</topic><topic>Monocytes</topic><topic>Monocytes - immunology</topic><topic>Original</topic><topic>original-article</topic><topic>Physiological aspects</topic><topic>Physiology</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Receptor, Serotonin, 5-HT2A - genetics</topic><topic>Rheumatoid arthritis</topic><topic>Rheumatology</topic><topic>Serotonin</topic><topic>Serotonin Receptor Agonists - pharmacology</topic><topic>Serotonin receptors</topic><topic>Serotonin S2 receptors</topic><topic>Single-nucleotide polymorphism</topic><topic>Smooth muscle</topic><topic>Staphylococcal enterotoxin B</topic><topic>T cells</topic><topic>T-Lymphocytes - immunology</topic><topic>Tumor necrosis factor- alpha</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><topic>Tumor necrosis factor-TNF</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Snir, O</creatorcontrib><creatorcontrib>Hesselberg, E</creatorcontrib><creatorcontrib>Amoudruz, P</creatorcontrib><creatorcontrib>Klareskog, L</creatorcontrib><creatorcontrib>Zarea-Ganji, I</creatorcontrib><creatorcontrib>Catrina, A I</creatorcontrib><creatorcontrib>Padyukov, L</creatorcontrib><creatorcontrib>Malmström, V</creatorcontrib><creatorcontrib>Seddighzadeh, M</creatorcontrib><collection>Springer_OA刊</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Biological Science Journals</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>Genes and immunity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Snir, O</au><au>Hesselberg, E</au><au>Amoudruz, P</au><au>Klareskog, L</au><au>Zarea-Ganji, I</au><au>Catrina, A I</au><au>Padyukov, L</au><au>Malmström, V</au><au>Seddighzadeh, M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic variation in the serotonin receptor gene affects immune responses in rheumatoid arthritis</atitle><jtitle>Genes and immunity</jtitle><stitle>Genes Immun</stitle><addtitle>Genes Immun</addtitle><date>2013-03-01</date><risdate>2013</risdate><volume>14</volume><issue>2</issue><spage>83</spage><epage>89</epage><pages>83-89</pages><issn>1466-4879</issn><issn>1476-5470</issn><eissn>1476-5470</eissn><abstract>Many genetic variants associate with the risk of developing rheumatoid arthritis (RA); however, their functional roles are largely unknown. Here, we aimed to investigate whether the RA-associated serotonin receptor 2A (
HTR2A)
haplotype affects T-cell and monocyte functions. Patients with established RA (
n
=379) were genotyped for two single-nucleotide polymorphisms (SNPs) in the
HTR2A
locus, rs6314 and rs1328674, to define presence of the risk haplotype for each individual. Patients with and without the RA-associated TC haplotype were selected and T-cell and monocyte function was monitored following
in vitro
stimulations with staphylococcal enterotoxin B and lipopolysaccharide (LPS) using multiparameter flow cytometry. Within the cohort, 44 patients were heterozygous for the TC haplotype (11.6%) while none were homozygous. Upon stimulation, T cells from TC-carrier patients produced more proinflammatory cytokines (tumor necrosis factor alpha (TNF-α), interleukin-17 (IL-17) and interferon gamma (IFN-γ)) and monocytes produced higher levels of TNF-α compared with patients carrying the non-TC haplotype (
P
<0.05 and 0.01, respectively). Such cytokine production could be inhibited in the presence of the selective 5-HT2 receptor agonist (2,5-Dimethoxy-4-iodoamphetamine, DOI); interestingly, this effect was more pronounced in TC carriers. Our data demonstrate that association of RA with a distinct serotonin receptor haplotype has functional impact by affecting the immunological phenotype of T cells and monocytes.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>23254357</pmid><doi>10.1038/gene.2012.56</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1466-4879 |
| ispartof | Genes and immunity, 2013-03, Vol.14 (2), p.83-89 |
| issn | 1466-4879 1476-5470 1476-5470 |
| language | eng |
| recordid | cdi_swepub_primary_oai_swepub_ki_se_532636 |
| source | MEDLINE; SWEPUB Freely available online; Free E-Journal (出版社公開部分のみ）; Alma/SFX Local Collection |
| subjects | 631/208/726/649 631/250/248 692/699/249/1313/498 Adult Aged Aged, 80 and over Amphetamines - pharmacology Arthritis, Rheumatoid - genetics Arthritis, Rheumatoid - immunology Biomedical and Life Sciences Biomedicine Cancer Research Cytokines Data processing Enterotoxins - immunology Flow cytometry gamma -Interferon Gene Expression Gene loci Genetic aspects Genetic diversity Genetic Variation Genomes Genotype Haplotypes Health aspects Human Genetics Humans Immune response Immunology Inflammation Interferon-gamma - metabolism Interleukin 17 Interleukin-17 - metabolism Lipopolysaccharides Lipopolysaccharides - immunology Lymphocytes Lymphocytes T Medicin och hälsovetenskap Middle Aged Monocytes Monocytes - immunology Original original-article Physiological aspects Physiology Polymorphism, Single Nucleotide Receptor, Serotonin, 5-HT2A - genetics Rheumatoid arthritis Rheumatology Serotonin Serotonin Receptor Agonists - pharmacology Serotonin receptors Serotonin S2 receptors Single-nucleotide polymorphism Smooth muscle Staphylococcal enterotoxin B T cells T-Lymphocytes - immunology Tumor necrosis factor- alpha Tumor Necrosis Factor-alpha - metabolism Tumor necrosis factor-TNF |
| title | Genetic variation in the serotonin receptor gene affects immune responses in rheumatoid arthritis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-28T09%3A52%3A55IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_swepu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Genetic%20variation%20in%20the%20serotonin%20receptor%20gene%20affects%20immune%20responses%20in%20rheumatoid%20arthritis&rft.jtitle=Genes%20and%20immunity&rft.au=Snir,%20O&rft.date=2013-03-01&rft.volume=14&rft.issue=2&rft.spage=83&rft.epage=89&rft.pages=83-89&rft.issn=1466-4879&rft.eissn=1476-5470&rft_id=info:doi/10.1038/gene.2012.56&rft_dat=%3Cgale_swepu%3EA322563675%3C/gale_swepu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1314919747&rft_id=info:pmid/23254357&rft_galeid=A322563675&rfr_iscdi=true |