IL1RN VNTR and IL2-330 polymorphic genes are independently associated with chronic immune thrombocytopenia
Chronic Immune Thrombocytopenia (cITP) is an acquired immune-mediated disease associated with a T-helper cell type 1 (Th1) immune polarization, whose genetic risk factors, however, are largely unknown. We investigated polymorphisms in promoter regions of genes that code molecules involved in proinfl...
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| Veröffentlicht in: | British journal of haematology 2010-09, Vol.150 (6), p.679-684 |
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| creator | CAMARGOS ROCHA, Andreia Maria DE SOUZA, Cláudia AGUIAR ROCHA, Gifone FREIRE DE MELO, Fabricio BORGES SARAIVA, Isadora Sofia DIOGO CLEMENTINO, Nelma Cristina ABREU MARINO, Marília Campos MAGALHAES QUEIROZ, Dulciene Maria |
| description | Chronic Immune Thrombocytopenia (cITP) is an acquired immune-mediated disease associated with a T-helper cell type 1 (Th1) immune polarization, whose genetic risk factors, however, are largely unknown. We investigated polymorphisms in promoter regions of genes that code molecules involved in proinflammatory immune response [IL1B-31T/C, IL1RN variable number tandem repeats (VNTR), IL2-330T/G, and TNF-307G/A] as well as in genes that code Toll like receptors (TLR) (TLR2 Arg753Gln, TLR4 Asp299Gly and TLR5 Arg(392stop)) in 122 patients with cITP and 541 blood donors. The frequencies of the IL1RN polymorphic allele 2 (P = 0·001) and of the IL2-330 polymorphic allele G (P =0·004) were significantly higher in cITP patients than in blood donors. In logistic analysis adjusting for age and gender, the polymorphisms remained independently associated with cITP. Enhanced serum concentrations of interleukin (IL)-1α and IL-1β were observed in cITP (P < 10(-3) ) and blood donor (P = 0·04) carriers of the IL1RN*2. Also, the serum levels of IL-2 and γ-interferon (IFN-γ) were increased in cITP patients (P < 10(-3) and P = 0·04 respectively) and blood donors (P < 10(-3) and P = 0·03 respectively) harbouring the IL2-330G allele. Here we demonstrated that IL2-330G and IL1RN*2 are independently associated with cITP and are functional in vivo, which strongly suggests that they contribute to the pathogenesis of cITP. |
| doi_str_mv | 10.1111/j.1365-2141.2010.08318.x |
| format | Article |
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We investigated polymorphisms in promoter regions of genes that code molecules involved in proinflammatory immune response [IL1B-31T/C, IL1RN variable number tandem repeats (VNTR), IL2-330T/G, and TNF-307G/A] as well as in genes that code Toll like receptors (TLR) (TLR2 Arg753Gln, TLR4 Asp299Gly and TLR5 Arg(392stop)) in 122 patients with cITP and 541 blood donors. The frequencies of the IL1RN polymorphic allele 2 (P = 0·001) and of the IL2-330 polymorphic allele G (P =0·004) were significantly higher in cITP patients than in blood donors. In logistic analysis adjusting for age and gender, the polymorphisms remained independently associated with cITP. Enhanced serum concentrations of interleukin (IL)-1α and IL-1β were observed in cITP (P < 10(-3) ) and blood donor (P = 0·04) carriers of the IL1RN*2. Also, the serum levels of IL-2 and γ-interferon (IFN-γ) were increased in cITP patients (P < 10(-3) and P = 0·04 respectively) and blood donors (P < 10(-3) and P = 0·03 respectively) harbouring the IL2-330G allele. Here we demonstrated that IL2-330G and IL1RN*2 are independently associated with cITP and are functional in vivo, which strongly suggests that they contribute to the pathogenesis of cITP.</description><identifier>ISSN: 0007-1048</identifier><identifier>EISSN: 1365-2141</identifier><identifier>DOI: 10.1111/j.1365-2141.2010.08318.x</identifier><identifier>PMID: 20626741</identifier><identifier>CODEN: BJHEAL</identifier><language>eng</language><publisher>Oxford: Blackwell</publisher><subject>Adolescent ; Adult ; Age ; Aged ; Aged, 80 and over ; Biological and medical sciences ; Blood donors ; Chronic Disease ; Cytokines - blood ; Female ; g-Interferon ; gamma -Interferon ; Gene Frequency ; Gene polymorphism ; Genetic Predisposition to Disease ; Helper cells ; Hematologic and hematopoietic diseases ; Humans ; Immune response ; Inflammation ; Interleukin 1 ; Interleukin 1 Receptor Antagonist Protein - genetics ; Interleukin 2 ; Interleukin-2 - genetics ; Lymphocytes T ; Male ; Medical sciences ; Middle Aged ; Minisatellite Repeats ; Platelet diseases and coagulopathies ; Polarization ; Polymorphism, Genetic ; Promoters ; Prospective Studies ; Purpura, Thrombocytopenic, Idiopathic - genetics ; Purpura, Thrombocytopenic, Idiopathic - immunology ; Risk factors ; Serum levels ; Thrombocytopenia ; TLR2 protein ; TLR4 protein ; TLR5 protein ; Toll-like receptors ; Young Adult</subject><ispartof>British journal of haematology, 2010-09, Vol.150 (6), p.679-684</ispartof><rights>2015 INIST-CNRS</rights><rights>2010 Blackwell Publishing Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23222658$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20626741$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>CAMARGOS ROCHA, Andreia Maria</creatorcontrib><creatorcontrib>DE SOUZA, Cláudia</creatorcontrib><creatorcontrib>AGUIAR ROCHA, Gifone</creatorcontrib><creatorcontrib>FREIRE DE MELO, Fabricio</creatorcontrib><creatorcontrib>BORGES SARAIVA, Isadora Sofia</creatorcontrib><creatorcontrib>DIOGO CLEMENTINO, Nelma Cristina</creatorcontrib><creatorcontrib>ABREU MARINO, Marília Campos</creatorcontrib><creatorcontrib>MAGALHAES QUEIROZ, Dulciene Maria</creatorcontrib><title>IL1RN VNTR and IL2-330 polymorphic genes are independently associated with chronic immune thrombocytopenia</title><title>British journal of haematology</title><addtitle>Br J Haematol</addtitle><description>Chronic Immune Thrombocytopenia (cITP) is an acquired immune-mediated disease associated with a T-helper cell type 1 (Th1) immune polarization, whose genetic risk factors, however, are largely unknown. We investigated polymorphisms in promoter regions of genes that code molecules involved in proinflammatory immune response [IL1B-31T/C, IL1RN variable number tandem repeats (VNTR), IL2-330T/G, and TNF-307G/A] as well as in genes that code Toll like receptors (TLR) (TLR2 Arg753Gln, TLR4 Asp299Gly and TLR5 Arg(392stop)) in 122 patients with cITP and 541 blood donors. The frequencies of the IL1RN polymorphic allele 2 (P = 0·001) and of the IL2-330 polymorphic allele G (P =0·004) were significantly higher in cITP patients than in blood donors. In logistic analysis adjusting for age and gender, the polymorphisms remained independently associated with cITP. Enhanced serum concentrations of interleukin (IL)-1α and IL-1β were observed in cITP (P < 10(-3) ) and blood donor (P = 0·04) carriers of the IL1RN*2. Also, the serum levels of IL-2 and γ-interferon (IFN-γ) were increased in cITP patients (P < 10(-3) and P = 0·04 respectively) and blood donors (P < 10(-3) and P = 0·03 respectively) harbouring the IL2-330G allele. Here we demonstrated that IL2-330G and IL1RN*2 are independently associated with cITP and are functional in vivo, which strongly suggests that they contribute to the pathogenesis of cITP.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Age</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biological and medical sciences</subject><subject>Blood donors</subject><subject>Chronic Disease</subject><subject>Cytokines - blood</subject><subject>Female</subject><subject>g-Interferon</subject><subject>gamma -Interferon</subject><subject>Gene Frequency</subject><subject>Gene polymorphism</subject><subject>Genetic Predisposition to Disease</subject><subject>Helper cells</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>Immune response</subject><subject>Inflammation</subject><subject>Interleukin 1</subject><subject>Interleukin 1 Receptor Antagonist Protein - genetics</subject><subject>Interleukin 2</subject><subject>Interleukin-2 - genetics</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Minisatellite Repeats</subject><subject>Platelet diseases and coagulopathies</subject><subject>Polarization</subject><subject>Polymorphism, Genetic</subject><subject>Promoters</subject><subject>Prospective Studies</subject><subject>Purpura, Thrombocytopenic, Idiopathic - genetics</subject><subject>Purpura, Thrombocytopenic, Idiopathic - immunology</subject><subject>Risk factors</subject><subject>Serum levels</subject><subject>Thrombocytopenia</subject><subject>TLR2 protein</subject><subject>TLR4 protein</subject><subject>TLR5 protein</subject><subject>Toll-like receptors</subject><subject>Young Adult</subject><issn>0007-1048</issn><issn>1365-2141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1PwzAMhiMEYmPwF1AuiFOHnaRtekSIj0nTkKbBdUpTl2XqF00n2L8nEgOO-GDL9vNa8ssYR5hiiJvtFGUSRwIVTgWEKWiJevp5xMa_i2M2BoA0QlB6xM683wKghBhP2UhAIpJU4ZhtZ3NcLvjrYrXkpin4bC4iKYF3bbWv277bOMvfqCHPTU_cNQV1FFIzVHtuvG-tMwMV_MMNG243fdsE3tX1riE-hLbOW7sf2qBx5pydlKbydHGoE_bycL-6e4rmz4-zu9t51AkQQ0SUF8YqU2KagcKEUBPkOVCuY10KUiVialVSCpvFuSKRCQnaSIEJxtqgnLDr77td377vyA_r2nlLVWUaand-rcPjmRT6fzINLmmVaQjk5YHc5TUV6653ten36x8jA3B1AIy3pip701jn_zgphEhiLb8ASFiC-A</recordid><startdate>20100901</startdate><enddate>20100901</enddate><creator>CAMARGOS ROCHA, Andreia Maria</creator><creator>DE SOUZA, Cláudia</creator><creator>AGUIAR ROCHA, Gifone</creator><creator>FREIRE DE MELO, Fabricio</creator><creator>BORGES SARAIVA, Isadora Sofia</creator><creator>DIOGO CLEMENTINO, Nelma Cristina</creator><creator>ABREU MARINO, Marília Campos</creator><creator>MAGALHAES QUEIROZ, Dulciene Maria</creator><general>Blackwell</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope><scope>7T5</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20100901</creationdate><title>IL1RN VNTR and IL2-330 polymorphic genes are independently associated with chronic immune thrombocytopenia</title><author>CAMARGOS ROCHA, Andreia Maria ; DE SOUZA, Cláudia ; AGUIAR ROCHA, Gifone ; FREIRE DE MELO, Fabricio ; BORGES SARAIVA, Isadora Sofia ; DIOGO CLEMENTINO, Nelma Cristina ; ABREU MARINO, Marília Campos ; MAGALHAES QUEIROZ, Dulciene Maria</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p202t-eebdac4af1790416e18e0bb0eb858f2e4f117c46f2c95b4e292308a3216158a13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Age</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biological and medical sciences</topic><topic>Blood donors</topic><topic>Chronic Disease</topic><topic>Cytokines - blood</topic><topic>Female</topic><topic>g-Interferon</topic><topic>gamma -Interferon</topic><topic>Gene Frequency</topic><topic>Gene polymorphism</topic><topic>Genetic Predisposition to Disease</topic><topic>Helper cells</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Humans</topic><topic>Immune response</topic><topic>Inflammation</topic><topic>Interleukin 1</topic><topic>Interleukin 1 Receptor Antagonist Protein - genetics</topic><topic>Interleukin 2</topic><topic>Interleukin-2 - genetics</topic><topic>Lymphocytes T</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Minisatellite Repeats</topic><topic>Platelet diseases and coagulopathies</topic><topic>Polarization</topic><topic>Polymorphism, Genetic</topic><topic>Promoters</topic><topic>Prospective Studies</topic><topic>Purpura, Thrombocytopenic, Idiopathic - genetics</topic><topic>Purpura, Thrombocytopenic, Idiopathic - immunology</topic><topic>Risk factors</topic><topic>Serum levels</topic><topic>Thrombocytopenia</topic><topic>TLR2 protein</topic><topic>TLR4 protein</topic><topic>TLR5 protein</topic><topic>Toll-like receptors</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>CAMARGOS ROCHA, Andreia Maria</creatorcontrib><creatorcontrib>DE SOUZA, Cláudia</creatorcontrib><creatorcontrib>AGUIAR ROCHA, Gifone</creatorcontrib><creatorcontrib>FREIRE DE MELO, Fabricio</creatorcontrib><creatorcontrib>BORGES SARAIVA, Isadora Sofia</creatorcontrib><creatorcontrib>DIOGO CLEMENTINO, Nelma Cristina</creatorcontrib><creatorcontrib>ABREU MARINO, Marília Campos</creatorcontrib><creatorcontrib>MAGALHAES QUEIROZ, Dulciene Maria</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>British journal of haematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>CAMARGOS ROCHA, Andreia Maria</au><au>DE SOUZA, Cláudia</au><au>AGUIAR ROCHA, Gifone</au><au>FREIRE DE MELO, Fabricio</au><au>BORGES SARAIVA, Isadora Sofia</au><au>DIOGO CLEMENTINO, Nelma Cristina</au><au>ABREU MARINO, Marília Campos</au><au>MAGALHAES QUEIROZ, Dulciene Maria</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>IL1RN VNTR and IL2-330 polymorphic genes are independently associated with chronic immune thrombocytopenia</atitle><jtitle>British journal of haematology</jtitle><addtitle>Br J Haematol</addtitle><date>2010-09-01</date><risdate>2010</risdate><volume>150</volume><issue>6</issue><spage>679</spage><epage>684</epage><pages>679-684</pages><issn>0007-1048</issn><eissn>1365-2141</eissn><coden>BJHEAL</coden><abstract>Chronic Immune Thrombocytopenia (cITP) is an acquired immune-mediated disease associated with a T-helper cell type 1 (Th1) immune polarization, whose genetic risk factors, however, are largely unknown. We investigated polymorphisms in promoter regions of genes that code molecules involved in proinflammatory immune response [IL1B-31T/C, IL1RN variable number tandem repeats (VNTR), IL2-330T/G, and TNF-307G/A] as well as in genes that code Toll like receptors (TLR) (TLR2 Arg753Gln, TLR4 Asp299Gly and TLR5 Arg(392stop)) in 122 patients with cITP and 541 blood donors. The frequencies of the IL1RN polymorphic allele 2 (P = 0·001) and of the IL2-330 polymorphic allele G (P =0·004) were significantly higher in cITP patients than in blood donors. In logistic analysis adjusting for age and gender, the polymorphisms remained independently associated with cITP. Enhanced serum concentrations of interleukin (IL)-1α and IL-1β were observed in cITP (P < 10(-3) ) and blood donor (P = 0·04) carriers of the IL1RN*2. Also, the serum levels of IL-2 and γ-interferon (IFN-γ) were increased in cITP patients (P < 10(-3) and P = 0·04 respectively) and blood donors (P < 10(-3) and P = 0·03 respectively) harbouring the IL2-330G allele. Here we demonstrated that IL2-330G and IL1RN*2 are independently associated with cITP and are functional in vivo, which strongly suggests that they contribute to the pathogenesis of cITP.</abstract><cop>Oxford</cop><pub>Blackwell</pub><pmid>20626741</pmid><doi>10.1111/j.1365-2141.2010.08318.x</doi><tpages>6</tpages></addata></record> |
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| subjects | Adolescent Adult Age Aged Aged, 80 and over Biological and medical sciences Blood donors Chronic Disease Cytokines - blood Female g-Interferon gamma -Interferon Gene Frequency Gene polymorphism Genetic Predisposition to Disease Helper cells Hematologic and hematopoietic diseases Humans Immune response Inflammation Interleukin 1 Interleukin 1 Receptor Antagonist Protein - genetics Interleukin 2 Interleukin-2 - genetics Lymphocytes T Male Medical sciences Middle Aged Minisatellite Repeats Platelet diseases and coagulopathies Polarization Polymorphism, Genetic Promoters Prospective Studies Purpura, Thrombocytopenic, Idiopathic - genetics Purpura, Thrombocytopenic, Idiopathic - immunology Risk factors Serum levels Thrombocytopenia TLR2 protein TLR4 protein TLR5 protein Toll-like receptors Young Adult |
| title | IL1RN VNTR and IL2-330 polymorphic genes are independently associated with chronic immune thrombocytopenia |
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