A common missense variant in the ATP receptor P2X7 is associated with reduced risk of cardiovascular events.
BACKGROUND AND PURPOSE: 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 h...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3360776?pdf=render |
| _version_ | 1818275207800946688 |
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| author | Olof Gidlöf J Gustav Smith Olle Melander Håkan Lövkvist Bo Hedblad Gunnar Engström Peter Nilsson Joyce Carlson Göran Berglund Sandra Olsson Katarina Jood Christina Jern Bo Norrving Arne Lindgren David Erlinge |
| author_facet | Olof Gidlöf J Gustav Smith Olle Melander Håkan Lövkvist Bo Hedblad Gunnar Engström Peter Nilsson Joyce Carlson Göran Berglund Sandra Olsson Katarina Jood Christina Jern Bo Norrving Arne Lindgren David Erlinge |
| author_sort | Olof Gidlöf |
| collection | DOAJ |
| description | BACKGROUND AND PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. |
| first_indexed | 2024-12-12T22:26:05Z |
| format | Article |
| id | doaj.art-7c7d97321bad48b787d316ef98ebac3d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T22:26:05Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-7c7d97321bad48b787d316ef98ebac3d2022-12-22T00:09:45ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0175e3749110.1371/journal.pone.0037491A common missense variant in the ATP receptor P2X7 is associated with reduced risk of cardiovascular events.Olof GidlöfJ Gustav SmithOlle MelanderHåkan LövkvistBo HedbladGunnar EngströmPeter NilssonJoyce CarlsonGöran BerglundSandra OlssonKatarina JoodChristina JernBo NorrvingArne LindgrenDavid ErlingeBACKGROUND AND PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.http://europepmc.org/articles/PMC3360776?pdf=render |
| spellingShingle | Olof Gidlöf J Gustav Smith Olle Melander Håkan Lövkvist Bo Hedblad Gunnar Engström Peter Nilsson Joyce Carlson Göran Berglund Sandra Olsson Katarina Jood Christina Jern Bo Norrving Arne Lindgren David Erlinge A common missense variant in the ATP receptor P2X7 is associated with reduced risk of cardiovascular events. PLoS ONE |
| title | A common missense variant in the ATP receptor P2X7 is associated with reduced risk of cardiovascular events. |
| title_full | A common missense variant in the ATP receptor P2X7 is associated with reduced risk of cardiovascular events. |
| title_fullStr | A common missense variant in the ATP receptor P2X7 is associated with reduced risk of cardiovascular events. |
| title_full_unstemmed | A common missense variant in the ATP receptor P2X7 is associated with reduced risk of cardiovascular events. |
| title_short | A common missense variant in the ATP receptor P2X7 is associated with reduced risk of cardiovascular events. |
| title_sort | common missense variant in the atp receptor p2x7 is associated with reduced risk of cardiovascular events |
| url | http://europepmc.org/articles/PMC3360776?pdf=render |
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