Polymorphisms of prostaglandin-endoperoxide synthase 2 gene, and prostaglandin-E receptor 2 gene, C-reactive protein concentrations and risk of atherothrombosis: a nested case-control approach.
OBJECTIVE
Recent data have shown an association between polymorphisms of prostaglandin-endoperoxide synthase-2 gene (PTGS2; alias COX-2), and prostaglandin-E receptor-2 gene (PTGER2) and risk of atherothrombotic disorders.


METHODS
We evaluated two PTGS2 (rs20417, rs689470), and three PTGER2 (rs708494/uS5, rs708495/uS7, and chr14: 50 764 013/uS10) gene polymorphisms among 600 Caucasian male participants of the Physicians' Health Study with incident myocardial infarction (MI) or ischemic stroke and 600 age- and smoking-matched controls who remained free of all reported cardiovascular disease.


RESULTS
Genotype distributions were in Hardy-Weinberg equilibrium in the control groups. Genotype and allele distribution were similar between cases and controls. The polymorphisms tested were in linkage disequilibrium. Results from the adjusted haplotype-based conditional logistic regression analysis showed a modest association of the PTGER2 2-1-1 haplotype with reduced risk of MI (odds ratio = 0.50, 95% CI; CI = 0.26-0.97, P = 0.04), and the 2-2-1 haplotype with reduced risk of ischemic stroke (odds ratio = 0.68, 95% CI = 0.47-0.99, P = 0.048). In contrast to prior data, we found no evidence for an association of the PTGS2 polymorphisms/haplotypes tested with risk of incident MI nor with ischemic stroke. However, we found suggestive evidence for an association of specific PTGER2 haplotypes with reduced risk of these outcomes.


CONCLUSIONS
Although these prospective data implicate the potential involvement of prostaglandin-E receptor-2 gene variation in atherothrombosis, external validation of our findings is needed.
Hegener
H H
HH
Center for Cardiovascular Disease Prevention, The Donald W. Reynolds Center for Cardiovascular Research, The Leducq Center for Molecular and Genetic Epidemiology, Boston, MA 02215, USA.
Diehl
K A
KA
Kurth
T
T
Gaziano
J M
JM
Ridker
P M
PM
Zee
R Y L
RY
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000494:pharmacology; D002097:C-Reactive Protein / Q000096:biosynthesis*; D016022:Case-Control Studies; D051546:Cyclooxygenase 2 / Q000235:genetics*; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D010919:Placebos; D011110:Polymorphism, Genetic; D018078:Receptors, Prostaglandin E / Q000235:genetics*; D013927:Thrombosis / Q000097:blood*; D019207:beta Carotene / Q000494:pharmacology
D008565:Membrane Proteins; D010919:Placebos; D018078:Receptors, Prostaglandin E; D019207:beta Carotene; D002097:C-Reactive Protein; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D001241:Aspirin