Variation in eicosanoid genes, non-fatal myocardial infarction and ischemic stroke.
OBJECTIVE
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.
Lemaitre
Rozenn N
RN
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA. rozenl@u.washington.edu
Rice
Kenneth
K
Marciante
Kristin
K
Bis
Joshua C
JC
Lumley
Thomas S
TS
Wiggins
Kerri L
KL
Smith
Nicholas L
NL
Heckbert
Susan R
SR
Psaty
Bruce M
BM
D000328:Adult; D000368:Aged; D001091:Arachidonate Lipoxygenases / Q000235:genetics; D001241:Aspirin / Q000627:therapeutic use; D002545:Brain Ischemia / Q000201:enzymology / Q000235:genetics* / Q000517:prevention & control; D016022:Case-Control Studies; D051545:Cyclooxygenase 1 / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D015777:Eicosanoids / Q000378:metabolism*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000201:enzymology / Q000235:genetics* / Q000517:prevention & control; D016017:Odds Ratio; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D000071876:Prostaglandin-E Synthases; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000201:enzymology / Q000235:genetics* / Q000517:prevention & control; D013930:Thromboxane-A Synthase / Q000235:genetics*
D015777:Eicosanoids; D010975:Platelet Aggregation Inhibitors; D003577:Cytochrome P-450 Enzyme System; D001091:Arachidonate Lipoxygenases; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases; C472456:PTGIS protein, human; D013930:Thromboxane-A Synthase; D001241:Aspirin