Document Detail


Variation in eicosanoid genes, non-fatal myocardial infarction and ischemic stroke.
MedLine Citation:
PMID:  19046748     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: Eicosanoids are lipid mediators that may play a role in atherosclerosis. We investigated the association of common genetic variation in prostaglandin H synthase 1 (PTGS1), prostaglandin H synthase 2 (PTGS2), thromboxane A2 synthase (TBXAS1), prostacyclin synthase (PTGIS), prostaglandin E synthase (PTGES), 5-lipoxygenase activating protein (ALOX5AP), 12-lipoxygenase (ALOX12) and 15-lipoxygenase (ALOX15) with the risks of myocardial infarction (MI) and ischemic stroke. A secondary aim was to replicate the interaction of PTGS2 rs20417 (-765G to C) with aspirin use on coronary heart disease risk observed in the Atherosclerosis Risk in Communities Study (ARIC).
METHODS: We conducted a case-control study in a large Health Maintenance Organization. Cases were men and women, aged 30-79 years with incident non-fatal myocardial infarction (n=1063) or ischemic stroke (n=469) between January 1995 and December 2004. Controls (n=3462) were randomly selected and frequency matched to cases on age, sex, hypertension and calendar year.
RESULTS: Common variation in TBXAS1 and PTGIS was associated with MI risk (p-value for global Chi-square test, 0.01 and 0.03, respectively). Common variation in ALOX5AP, ALOX12, ALOX15, PTGS1, PTGS2 and PTGES was not associated with risks of MI and ischemic stroke. We replicated the observation of the Atherosclerosis Risk in Communities Study and observed an interaction of rs20417 with aspirin use on myocardial infarction risk (p for interaction=0.03).
CONCLUSIONS: Study results suggest that variation in TBXAS1 and PTGIS may influence MI risk, and carriers of rs20417C allele might derive greater benefits from aspirin use in primary prevention.
Authors:
Rozenn N Lemaitre; Kenneth Rice; Kristin Marciante; Joshua C Bis; Thomas S Lumley; Kerri L Wiggins; Nicholas L Smith; Susan R Heckbert; Bruce M Psaty
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-11-01
Journal Detail:
Title:  Atherosclerosis     Volume:  204     ISSN:  1879-1484     ISO Abbreviation:  Atherosclerosis     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-05-25     Completed Date:  2009-08-10     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  0242543     Medline TA:  Atherosclerosis     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  e58-63     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Arachidonate Lipoxygenases / genetics
Aspirin / therapeutic use
Brain Ischemia / enzymology,  genetics*,  prevention & control
Case-Control Studies
Cyclooxygenase 1 / genetics
Cyclooxygenase 2 / genetics
Cytochrome P-450 Enzyme System / genetics*
Eicosanoids / metabolism*
Female
Gene Frequency
Genetic Predisposition to Disease
Humans
Intramolecular Oxidoreductases / genetics
Male
Middle Aged
Myocardial Infarction / enzymology,  genetics*,  prevention & control
Odds Ratio
Platelet Aggregation Inhibitors / therapeutic use
Polymorphism, Single Nucleotide*
Risk Assessment
Risk Factors
Stroke / enzymology,  genetics*,  prevention & control
Thromboxane-A Synthase / genetics*
Grant Support
ID/Acronym/Agency:
AG09556/AG/NIA NIH HHS; HL43201/HL/NHLBI NIH HHS; HL60739/HL/NHLBI NIH HHS; HL68639/HL/NHLBI NIH HHS; HL68986/HL/NHLBI NIH HHS; HL73410/HL/NHLBI NIH HHS; HL74745/HL/NHLBI NIH HHS; R01 AG009556/AG/NIA NIH HHS; R01 AG009556-05/AG/NIA NIH HHS; R01 HL043201/HL/NHLBI NIH HHS; R01 HL043201-13/HL/NHLBI NIH HHS; R01 HL060739/HL/NHLBI NIH HHS; R01 HL060739-04/HL/NHLBI NIH HHS; R01 HL068639/HL/NHLBI NIH HHS; R01 HL068639-04/HL/NHLBI NIH HHS; R01 HL068986/HL/NHLBI NIH HHS; R01 HL068986-04/HL/NHLBI NIH HHS; R01 HL073410-04/HL/NHLBI NIH HHS; R01 HL074745/HL/NHLBI NIH HHS; R01 HL074745-04/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Eicosanoids; 0/Platelet Aggregation Inhibitors; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.13.11.-/Arachidonate Lipoxygenases; EC 1.14.99.1/Cyclooxygenase 1; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/PTGS1 protein, human; EC 1.14.99.1/PTGS2 protein, human; EC 5.3.-/Intramolecular Oxidoreductases; EC 5.3.99.3/prostaglandin-E synthase; EC 5.3.99.4/PTGIS protein, human; EC 5.3.99.5/Thromboxane-A Synthase; R16CO5Y76E/Aspirin
Comments/Corrections

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