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...
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Published in | PloS one Vol. 7; no. 5; p. e37491 |
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Main Authors | , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Public Library of Science
25.05.2012
Public Library of Science (PLoS) |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Conceived and designed the experiments: OG JGS OM HL BH GE PN JC GB SO KJ CJ BN AL DE. Performed the experiments: OG JGS OM HL BH GE PN JC GB SO KJ CJ BN AL DE. Analyzed the data: OG JGS OM CJ BN AL DE. Contributed reagents/materials/analysis tools: OM HL BH GE PN JC GB KJ CJ BN AL DE. Wrote the paper: OG JGS AL DE. |
ISSN: | 1932-6203 1932-6203 |
DOI: | 10.1371/journal.pone.0037491 |