A common missense variant in the ATP receptor P2X7 is associated with reduced risk of cardiovascular events
Extracellular adenosine triphosphate (ATP) regulates inflammatory cells by activation of the P2X(7) receptor. We hypothesized that polymorphisms in P2RX7 influence the risk of ischemic heart disease (IHD), ischemic stroke (IS) and cardiovascular risk factors and tested this hypothesis using genetic...
Gespeichert in:
| Veröffentlicht in: | PloS one 2012-05, Vol.7 (5), p.e37491-e37491 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e37491 |
|---|---|
| container_issue | 5 |
| container_start_page | e37491 |
| container_title | PloS one |
| container_volume | 7 |
| creator | Gidlöf, Olof Smith, J Gustav Melander, Olle Lövkvist, Håkan Hedblad, Bo Engström, Gunnar Nilsson, Peter Carlson, Joyce Berglund, Göran Olsson, Sandra Jood, Katarina Jern, Christina Norrving, Bo Lindgren, Arne Erlinge, David |
| description | Extracellular adenosine triphosphate (ATP) regulates inflammatory cells by activation of the P2X(7) receptor. We hypothesized that polymorphisms in P2RX7 influence the risk of ischemic heart disease (IHD), ischemic stroke (IS) and cardiovascular risk factors and tested this hypothesis using genetic association studies.
Two loss-of-function SNPs in P2RX7 were genotyped in 1244 IHD cases and 2488 controls as well as 5969 individuals with cardiovascular risk factors. Eleven SNPs in a 250 kb region on chromosome 12 spanning P2RX7 as well as neighboring genes OASL, P2RX4 and CAMKK2 were genotyped in 4138 individuals with IS and 2528 controls. Association was examined using linear and logistic regression models with an additive genetic model.
The common loss-of-function variant rs3751143 was significantly associated with a decreased risk of IHD in smokers (P = 0.03) as well as decreased risk of IS (OR 0.89; 95% CI = 0.81-0.97; P = 0.012). In addition, an intronic SNP in CAMKK2, rs2686342, were associated with a decreased risk of IS (OR 0.89; 95% CI = 0.82-0.97; P = 0.011). In subgroup analyses, both SNPs were associated with decreased risk of IS in individuals with hypertension (P = 0.045 and 0.015, respectively).
A common loss-of-function missense variant in the gene encoding the P2X(7) receptor is associated with reduced risk of IS and with IHD in smokers. These findings might implicate a role of purinergic signaling in atherogenesis or atherothrombosis. |
| doi_str_mv | 10.1371/journal.pone.0037491 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1325012535</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A477041713</galeid><doaj_id>oai_doaj_org_article_7c7d97321bad48b787d316ef98ebac3d</doaj_id><sourcerecordid>A477041713</sourcerecordid><originalsourceid>FETCH-LOGICAL-c799t-3b2181572c80c77898daf655267f8bd6382a808b7cbe3f62f943a7b54593742c3</originalsourceid><addsrcrecordid>eNqNk11rFDEYhQdRbK3-A9GAIHqxaz5m8nEjLMWPQqFFq3gXMklmN-3sZE1mtvrvfbe7LTtSQYYwyTvPOWFO8hbFc4KnhAny7jIOqTPtdBU7P8WYiVKRB8UhUYxOOMXs4d78oHiS8yXGFZOcPy4OKOWcEo4Pi6sZsnG5jB1ahpx9lz1amxRM16PQoX7h0eziHCVv_aqPCZ3THwKFjEzO0QbTe4euQ78AwA0WFinkKxQbZE1yIa5NtkNrEvJr3_X5afGoMW32z3bvo-Lbxw8Xx58np2efTo5npxMrlOonrKZEkkpQK7EVQirpTMOrinLRyNpxJqmRWNbC1p41nDaqZEbUVVkpCIFadlS83Pqu2pj1LqesCaMVJrRiFRAnW8JFc6lXKSxN-q2jCfqmENNcm9QH23otrHBKMEpq40rYVArHCPeNkr42ljnwOt165Wu_GuqRWzusYNQwdPa6tLTkilJNbKlgJZ2uK2a1ssI2TDVEcQl2k3_azcEOSvMbNzg-VZXAv9_97FAvvbMQdDLtSDb-0oWFnse1ZoxjITgYvNkZpPhz8LnXcBOsb1vT-ThAbJhIzigkAOirv9D7w91RcwP5ha6JsK_dmOpZKQQuiSAMqOk9FDzOL4OFO90EqI8Eb0cCYHr_q5-bIWd98vXL_7Nn38fs6z124U3bL3Jshz7ELo_BcgvaFHNOvrkLmWC9acnbNPSmJfWuJUH2Yv-A7kS3Pcj-AGteL9Y</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1325012535</pqid></control><display><type>article</type><title>A common missense variant in the ATP receptor P2X7 is associated with reduced risk of cardiovascular events</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>SWEPUB Freely available online</source><source>Public Library of Science (PLoS)</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Gidlöf, Olof ; Smith, J Gustav ; Melander, Olle ; Lövkvist, Håkan ; Hedblad, Bo ; Engström, Gunnar ; Nilsson, Peter ; Carlson, Joyce ; Berglund, Göran ; Olsson, Sandra ; Jood, Katarina ; Jern, Christina ; Norrving, Bo ; Lindgren, Arne ; Erlinge, David</creator><contributor>Zhang, Weili</contributor><creatorcontrib>Gidlöf, Olof ; Smith, J Gustav ; Melander, Olle ; Lövkvist, Håkan ; Hedblad, Bo ; Engström, Gunnar ; Nilsson, Peter ; Carlson, Joyce ; Berglund, Göran ; Olsson, Sandra ; Jood, Katarina ; Jern, Christina ; Norrving, Bo ; Lindgren, Arne ; Erlinge, David ; Zhang, Weili</creatorcontrib><description>Extracellular adenosine triphosphate (ATP) regulates inflammatory cells by activation of the P2X(7) receptor. We hypothesized that polymorphisms in P2RX7 influence the risk of ischemic heart disease (IHD), ischemic stroke (IS) and cardiovascular risk factors and tested this hypothesis using genetic association studies.
Two loss-of-function SNPs in P2RX7 were genotyped in 1244 IHD cases and 2488 controls as well as 5969 individuals with cardiovascular risk factors. Eleven SNPs in a 250 kb region on chromosome 12 spanning P2RX7 as well as neighboring genes OASL, P2RX4 and CAMKK2 were genotyped in 4138 individuals with IS and 2528 controls. Association was examined using linear and logistic regression models with an additive genetic model.
The common loss-of-function variant rs3751143 was significantly associated with a decreased risk of IHD in smokers (P = 0.03) as well as decreased risk of IS (OR 0.89; 95% CI = 0.81-0.97; P = 0.012). In addition, an intronic SNP in CAMKK2, rs2686342, were associated with a decreased risk of IS (OR 0.89; 95% CI = 0.82-0.97; P = 0.011). In subgroup analyses, both SNPs were associated with decreased risk of IS in individuals with hypertension (P = 0.045 and 0.015, respectively).
A common loss-of-function missense variant in the gene encoding the P2X(7) receptor is associated with reduced risk of IS and with IHD in smokers. These findings might implicate a role of purinergic signaling in atherogenesis or atherothrombosis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0037491</identifier><identifier>PMID: 22662160</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenosine triphosphate ; Adenosine Triphosphate - metabolism ; Aged ; Aged, 80 and over ; Atherogenesis ; atherosclerosis ; ATP ; ATP (Adenosine triphosphate) ; Biology ; Biomarkers ; blood-pressure ; Cardiac and Cardiovascular Systems ; Cardiovascular disease ; Cardiovascular diseases ; Cardiovascular Diseases - genetics ; Chromosome 12 ; Clinical Medicine ; Coronary artery disease ; Cytokines ; Diabetes ; disease ; Female ; gain-of-function ; Gene Frequency ; Gene Order ; Genes ; Genetic aspects ; genetic association ; Genetic Predisposition to Disease ; Genotype ; Haplotypes ; Health risks ; Heart ; Heart diseases ; human p2x receptor ; Humans ; Hypertension ; Inflammation ; Ischemia ; ischemic-stroke ; Kardiologi ; Kinases ; Klinisk medicin ; Linkage Disequilibrium ; Lymphocytes ; Male ; Medical and Health Sciences ; Medicin och hälsovetenskap ; Medicine ; Middle Aged ; Multiple sclerosis ; Muscle proteins ; Mutation, Missense ; Neurosciences ; Physiology ; Polymorphism ; Polymorphism, Single Nucleotide ; Proteins ; Quality Control ; Receptors, Purinergic P2X7 - genetics ; Receptors, Purinergic P2X7 - metabolism ; Regression analysis ; Regression models ; Rehabilitation ; Risk ; Risk analysis ; Risk factors ; Signaling ; Single-nucleotide polymorphism ; Stroke ; Studies ; susceptibility ; Thrombosis ; Toxoplasma gondii ; Ultrasonic imaging</subject><ispartof>PloS one, 2012-05, Vol.7 (5), p.e37491-e37491</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Gidlöf et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Gidlöf et al. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c799t-3b2181572c80c77898daf655267f8bd6382a808b7cbe3f62f943a7b54593742c3</citedby><cites>FETCH-LOGICAL-c799t-3b2181572c80c77898daf655267f8bd6382a808b7cbe3f62f943a7b54593742c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3360776/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3360776/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,553,728,781,785,865,886,2103,2929,23871,27929,27930,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22662160$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://gup.ub.gu.se/publication/160954$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttps://lup.lub.lu.se/record/2859840$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><contributor>Zhang, Weili</contributor><creatorcontrib>Gidlöf, Olof</creatorcontrib><creatorcontrib>Smith, J Gustav</creatorcontrib><creatorcontrib>Melander, Olle</creatorcontrib><creatorcontrib>Lövkvist, Håkan</creatorcontrib><creatorcontrib>Hedblad, Bo</creatorcontrib><creatorcontrib>Engström, Gunnar</creatorcontrib><creatorcontrib>Nilsson, Peter</creatorcontrib><creatorcontrib>Carlson, Joyce</creatorcontrib><creatorcontrib>Berglund, Göran</creatorcontrib><creatorcontrib>Olsson, Sandra</creatorcontrib><creatorcontrib>Jood, Katarina</creatorcontrib><creatorcontrib>Jern, Christina</creatorcontrib><creatorcontrib>Norrving, Bo</creatorcontrib><creatorcontrib>Lindgren, Arne</creatorcontrib><creatorcontrib>Erlinge, David</creatorcontrib><title>A common missense variant in the ATP receptor P2X7 is associated with reduced risk of cardiovascular events</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Extracellular adenosine triphosphate (ATP) regulates inflammatory cells by activation of the P2X(7) receptor. We hypothesized that polymorphisms in P2RX7 influence the risk of ischemic heart disease (IHD), ischemic stroke (IS) and cardiovascular risk factors and tested this hypothesis using genetic association studies.
Two loss-of-function SNPs in P2RX7 were genotyped in 1244 IHD cases and 2488 controls as well as 5969 individuals with cardiovascular risk factors. Eleven SNPs in a 250 kb region on chromosome 12 spanning P2RX7 as well as neighboring genes OASL, P2RX4 and CAMKK2 were genotyped in 4138 individuals with IS and 2528 controls. Association was examined using linear and logistic regression models with an additive genetic model.
The common loss-of-function variant rs3751143 was significantly associated with a decreased risk of IHD in smokers (P = 0.03) as well as decreased risk of IS (OR 0.89; 95% CI = 0.81-0.97; P = 0.012). In addition, an intronic SNP in CAMKK2, rs2686342, were associated with a decreased risk of IS (OR 0.89; 95% CI = 0.82-0.97; P = 0.011). In subgroup analyses, both SNPs were associated with decreased risk of IS in individuals with hypertension (P = 0.045 and 0.015, respectively).
A common loss-of-function missense variant in the gene encoding the P2X(7) receptor is associated with reduced risk of IS and with IHD in smokers. These findings might implicate a role of purinergic signaling in atherogenesis or atherothrombosis.</description><subject>Adenosine triphosphate</subject><subject>Adenosine Triphosphate - metabolism</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Atherogenesis</subject><subject>atherosclerosis</subject><subject>ATP</subject><subject>ATP (Adenosine triphosphate)</subject><subject>Biology</subject><subject>Biomarkers</subject><subject>blood-pressure</subject><subject>Cardiac and Cardiovascular Systems</subject><subject>Cardiovascular disease</subject><subject>Cardiovascular diseases</subject><subject>Cardiovascular Diseases - genetics</subject><subject>Chromosome 12</subject><subject>Clinical Medicine</subject><subject>Coronary artery disease</subject><subject>Cytokines</subject><subject>Diabetes</subject><subject>disease</subject><subject>Female</subject><subject>gain-of-function</subject><subject>Gene Frequency</subject><subject>Gene Order</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>genetic association</subject><subject>Genetic Predisposition to Disease</subject><subject>Genotype</subject><subject>Haplotypes</subject><subject>Health risks</subject><subject>Heart</subject><subject>Heart diseases</subject><subject>human p2x receptor</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Inflammation</subject><subject>Ischemia</subject><subject>ischemic-stroke</subject><subject>Kardiologi</subject><subject>Kinases</subject><subject>Klinisk medicin</subject><subject>Linkage Disequilibrium</subject><subject>Lymphocytes</subject><subject>Male</subject><subject>Medical and Health Sciences</subject><subject>Medicin och hälsovetenskap</subject><subject>Medicine</subject><subject>Middle Aged</subject><subject>Multiple sclerosis</subject><subject>Muscle proteins</subject><subject>Mutation, Missense</subject><subject>Neurosciences</subject><subject>Physiology</subject><subject>Polymorphism</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Proteins</subject><subject>Quality Control</subject><subject>Receptors, Purinergic P2X7 - genetics</subject><subject>Receptors, Purinergic P2X7 - metabolism</subject><subject>Regression analysis</subject><subject>Regression models</subject><subject>Rehabilitation</subject><subject>Risk</subject><subject>Risk analysis</subject><subject>Risk factors</subject><subject>Signaling</subject><subject>Single-nucleotide polymorphism</subject><subject>Stroke</subject><subject>Studies</subject><subject>susceptibility</subject><subject>Thrombosis</subject><subject>Toxoplasma gondii</subject><subject>Ultrasonic imaging</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><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><sourceid>DOA</sourceid><recordid>eNqNk11rFDEYhQdRbK3-A9GAIHqxaz5m8nEjLMWPQqFFq3gXMklmN-3sZE1mtvrvfbe7LTtSQYYwyTvPOWFO8hbFc4KnhAny7jIOqTPtdBU7P8WYiVKRB8UhUYxOOMXs4d78oHiS8yXGFZOcPy4OKOWcEo4Pi6sZsnG5jB1ahpx9lz1amxRM16PQoX7h0eziHCVv_aqPCZ3THwKFjEzO0QbTe4euQ78AwA0WFinkKxQbZE1yIa5NtkNrEvJr3_X5afGoMW32z3bvo-Lbxw8Xx58np2efTo5npxMrlOonrKZEkkpQK7EVQirpTMOrinLRyNpxJqmRWNbC1p41nDaqZEbUVVkpCIFadlS83Pqu2pj1LqesCaMVJrRiFRAnW8JFc6lXKSxN-q2jCfqmENNcm9QH23otrHBKMEpq40rYVArHCPeNkr42ljnwOt165Wu_GuqRWzusYNQwdPa6tLTkilJNbKlgJZ2uK2a1ssI2TDVEcQl2k3_azcEOSvMbNzg-VZXAv9_97FAvvbMQdDLtSDb-0oWFnse1ZoxjITgYvNkZpPhz8LnXcBOsb1vT-ThAbJhIzigkAOirv9D7w91RcwP5ha6JsK_dmOpZKQQuiSAMqOk9FDzOL4OFO90EqI8Eb0cCYHr_q5-bIWd98vXL_7Nn38fs6z124U3bL3Jshz7ELo_BcgvaFHNOvrkLmWC9acnbNPSmJfWuJUH2Yv-A7kS3Pcj-AGteL9Y</recordid><startdate>20120525</startdate><enddate>20120525</enddate><creator>Gidlöf, Olof</creator><creator>Smith, J Gustav</creator><creator>Melander, Olle</creator><creator>Lövkvist, Håkan</creator><creator>Hedblad, Bo</creator><creator>Engström, Gunnar</creator><creator>Nilsson, Peter</creator><creator>Carlson, Joyce</creator><creator>Berglund, Göran</creator><creator>Olsson, Sandra</creator><creator>Jood, Katarina</creator><creator>Jern, Christina</creator><creator>Norrving, Bo</creator><creator>Lindgren, Arne</creator><creator>Erlinge, David</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</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>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>F1U</scope><scope>AGCHP</scope><scope>D8T</scope><scope>D95</scope><scope>ZZAVC</scope><scope>DOA</scope></search><sort><creationdate>20120525</creationdate><title>A common missense variant in the ATP receptor P2X7 is associated with reduced risk of cardiovascular events</title><author>Gidlöf, Olof ; Smith, J Gustav ; Melander, Olle ; Lövkvist, Håkan ; Hedblad, Bo ; Engström, Gunnar ; Nilsson, Peter ; Carlson, Joyce ; Berglund, Göran ; Olsson, Sandra ; Jood, Katarina ; Jern, Christina ; Norrving, Bo ; Lindgren, Arne ; Erlinge, David</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c799t-3b2181572c80c77898daf655267f8bd6382a808b7cbe3f62f943a7b54593742c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adenosine triphosphate</topic><topic>Adenosine Triphosphate - metabolism</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Atherogenesis</topic><topic>atherosclerosis</topic><topic>ATP</topic><topic>ATP (Adenosine triphosphate)</topic><topic>Biology</topic><topic>Biomarkers</topic><topic>blood-pressure</topic><topic>Cardiac and Cardiovascular Systems</topic><topic>Cardiovascular disease</topic><topic>Cardiovascular diseases</topic><topic>Cardiovascular Diseases - genetics</topic><topic>Chromosome 12</topic><topic>Clinical Medicine</topic><topic>Coronary artery disease</topic><topic>Cytokines</topic><topic>Diabetes</topic><topic>disease</topic><topic>Female</topic><topic>gain-of-function</topic><topic>Gene Frequency</topic><topic>Gene Order</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>genetic association</topic><topic>Genetic Predisposition to Disease</topic><topic>Genotype</topic><topic>Haplotypes</topic><topic>Health risks</topic><topic>Heart</topic><topic>Heart diseases</topic><topic>human p2x receptor</topic><topic>Humans</topic><topic>Hypertension</topic><topic>Inflammation</topic><topic>Ischemia</topic><topic>ischemic-stroke</topic><topic>Kardiologi</topic><topic>Kinases</topic><topic>Klinisk medicin</topic><topic>Linkage Disequilibrium</topic><topic>Lymphocytes</topic><topic>Male</topic><topic>Medical and Health Sciences</topic><topic>Medicin och hälsovetenskap</topic><topic>Medicine</topic><topic>Middle Aged</topic><topic>Multiple sclerosis</topic><topic>Muscle proteins</topic><topic>Mutation, Missense</topic><topic>Neurosciences</topic><topic>Physiology</topic><topic>Polymorphism</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Proteins</topic><topic>Quality Control</topic><topic>Receptors, Purinergic P2X7 - genetics</topic><topic>Receptors, Purinergic P2X7 - metabolism</topic><topic>Regression analysis</topic><topic>Regression models</topic><topic>Rehabilitation</topic><topic>Risk</topic><topic>Risk analysis</topic><topic>Risk factors</topic><topic>Signaling</topic><topic>Single-nucleotide polymorphism</topic><topic>Stroke</topic><topic>Studies</topic><topic>susceptibility</topic><topic>Thrombosis</topic><topic>Toxoplasma gondii</topic><topic>Ultrasonic imaging</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gidlöf, Olof</creatorcontrib><creatorcontrib>Smith, J Gustav</creatorcontrib><creatorcontrib>Melander, Olle</creatorcontrib><creatorcontrib>Lövkvist, Håkan</creatorcontrib><creatorcontrib>Hedblad, Bo</creatorcontrib><creatorcontrib>Engström, Gunnar</creatorcontrib><creatorcontrib>Nilsson, Peter</creatorcontrib><creatorcontrib>Carlson, Joyce</creatorcontrib><creatorcontrib>Berglund, Göran</creatorcontrib><creatorcontrib>Olsson, Sandra</creatorcontrib><creatorcontrib>Jood, Katarina</creatorcontrib><creatorcontrib>Jern, Christina</creatorcontrib><creatorcontrib>Norrving, Bo</creatorcontrib><creatorcontrib>Lindgren, Arne</creatorcontrib><creatorcontrib>Erlinge, David</creatorcontrib><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: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</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 Technology 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>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</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>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Access via ProQuest (Open Access)</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>Engineering Collection</collection><collection>Environmental Science Collection</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 Göteborgs universitet</collection><collection>SWEPUB Lunds universitet full text</collection><collection>SWEPUB Freely available online</collection><collection>SWEPUB Lunds universitet</collection><collection>SwePub Articles full text</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gidlöf, Olof</au><au>Smith, J Gustav</au><au>Melander, Olle</au><au>Lövkvist, Håkan</au><au>Hedblad, Bo</au><au>Engström, Gunnar</au><au>Nilsson, Peter</au><au>Carlson, Joyce</au><au>Berglund, Göran</au><au>Olsson, Sandra</au><au>Jood, Katarina</au><au>Jern, Christina</au><au>Norrving, Bo</au><au>Lindgren, Arne</au><au>Erlinge, David</au><au>Zhang, Weili</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A common missense variant in the ATP receptor P2X7 is associated with reduced risk of cardiovascular events</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-05-25</date><risdate>2012</risdate><volume>7</volume><issue>5</issue><spage>e37491</spage><epage>e37491</epage><pages>e37491-e37491</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Extracellular adenosine triphosphate (ATP) regulates inflammatory cells by activation of the P2X(7) receptor. We hypothesized that polymorphisms in P2RX7 influence the risk of ischemic heart disease (IHD), ischemic stroke (IS) and cardiovascular risk factors and tested this hypothesis using genetic association studies.
Two loss-of-function SNPs in P2RX7 were genotyped in 1244 IHD cases and 2488 controls as well as 5969 individuals with cardiovascular risk factors. Eleven SNPs in a 250 kb region on chromosome 12 spanning P2RX7 as well as neighboring genes OASL, P2RX4 and CAMKK2 were genotyped in 4138 individuals with IS and 2528 controls. Association was examined using linear and logistic regression models with an additive genetic model.
The common loss-of-function variant rs3751143 was significantly associated with a decreased risk of IHD in smokers (P = 0.03) as well as decreased risk of IS (OR 0.89; 95% CI = 0.81-0.97; P = 0.012). In addition, an intronic SNP in CAMKK2, rs2686342, were associated with a decreased risk of IS (OR 0.89; 95% CI = 0.82-0.97; P = 0.011). In subgroup analyses, both SNPs were associated with decreased risk of IS in individuals with hypertension (P = 0.045 and 0.015, respectively).
A common loss-of-function missense variant in the gene encoding the P2X(7) receptor is associated with reduced risk of IS and with IHD in smokers. These findings might implicate a role of purinergic signaling in atherogenesis or atherothrombosis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22662160</pmid><doi>10.1371/journal.pone.0037491</doi><tpages>e37491</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2012-05, Vol.7 (5), p.e37491-e37491 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1325012535 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; SWEPUB Freely available online; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adenosine triphosphate Adenosine Triphosphate - metabolism Aged Aged, 80 and over Atherogenesis atherosclerosis ATP ATP (Adenosine triphosphate) Biology Biomarkers blood-pressure Cardiac and Cardiovascular Systems Cardiovascular disease Cardiovascular diseases Cardiovascular Diseases - genetics Chromosome 12 Clinical Medicine Coronary artery disease Cytokines Diabetes disease Female gain-of-function Gene Frequency Gene Order Genes Genetic aspects genetic association Genetic Predisposition to Disease Genotype Haplotypes Health risks Heart Heart diseases human p2x receptor Humans Hypertension Inflammation Ischemia ischemic-stroke Kardiologi Kinases Klinisk medicin Linkage Disequilibrium Lymphocytes Male Medical and Health Sciences Medicin och hälsovetenskap Medicine Middle Aged Multiple sclerosis Muscle proteins Mutation, Missense Neurosciences Physiology Polymorphism Polymorphism, Single Nucleotide Proteins Quality Control Receptors, Purinergic P2X7 - genetics Receptors, Purinergic P2X7 - metabolism Regression analysis Regression models Rehabilitation Risk Risk analysis Risk factors Signaling Single-nucleotide polymorphism Stroke Studies susceptibility Thrombosis Toxoplasma gondii Ultrasonic imaging |
| title | A common missense variant in the ATP receptor P2X7 is associated with reduced risk of cardiovascular events |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-14T05%3A50%3A15IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20common%20missense%20variant%20in%20the%20ATP%20receptor%20P2X7%20is%20associated%20with%20reduced%20risk%20of%20cardiovascular%20events&rft.jtitle=PloS%20one&rft.au=Gidl%C3%B6f,%20Olof&rft.date=2012-05-25&rft.volume=7&rft.issue=5&rft.spage=e37491&rft.epage=e37491&rft.pages=e37491-e37491&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0037491&rft_dat=%3Cgale_plos_%3EA477041713%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1325012535&rft_id=info:pmid/22662160&rft_galeid=A477041713&rft_doaj_id=oai_doaj_org_article_7c7d97321bad48b787d316ef98ebac3d&rfr_iscdi=true |