Protective effect of the G-765C COX-2 polymorphism on subclinical atherosclerosis and inflammatory markers in asymptomatic subjects with cardiovascular risk factors.
BACKGROUND
Cyclooxygenase (COX)-2, a key regulatory enzyme in prostanoid synthesis, plays an important role in inflammatory processes. The -765G>C COX-2 polymorphism has been associated with lower promoter activity in vitro and reduced levels of C-reactive protein (CRP) in atherosclerotic carriers of the C allele. However, its pathophysiological relevance in vivo has not been fully elucidated.


RESULTS
We assessed the -765G>C polymorphism and COX-2 expression in 220 asymptomatic subjects free of cardiovascular disease, in relation to global vascular risk, carotid intima-media thickness (IMT), and inflammatory markers (fibrinogen, C-reactive protein [CRP], von Willebrand factor [vWF] and interleukin-6 [IL-6]). Genotype frequencies were: CC (7.7%), CG (34.5%), GG (57.7%). Among hypercholesterolemic subjects (n=140), C allele carriers had lower COX-2 expression (p<0.05), reduced carotid IMT (p<0.01) and diminished levels of inflammatory markers CRP, vWF and IL-6 (p<0.05), as compared to GG homozygous subjects. The association between carotid IMT and COX-2 polymorphism remained significant after adjusting for cardiovascular risk factors and inflammatory markers (p=0.008).


CONCLUSIONS
In asymptomatic hypercholesterolemic subjects the C allele of -765G>C COX-2 polymorphism was associated with lower COX-2 expression, and reduced subclinical atherosclerosis and systemic inflammation compared with GG homozygous, thus conferring atherosclerosis protection in this cardiovascular risk population.
Orbe
J
J
Atherosclerosis Research Laboratory, Division of Cardiovascular Science, Center for Applied Medical Research, Pamplona, Spain. josuneor@unav.es
Beloqui
O
O
Rodriguez
J A
JA
Belzunce
M S
MS
Roncal
C
C
Páramo
J A
JA
D050197:Atherosclerosis / Q000145:classification / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics*; D015415:Biomarkers; D002784:Cholesterol / Q000097:blood; D051546:Cyclooxygenase 2 / Q000235:genetics*; D003545:Cysteine / Q000235:genetics*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D020022:Genetic Predisposition to Disease; D005998:Glycine / Q000235:genetics*; D006801:Humans; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000201:enzymology; D011110:Polymorphism, Genetic / Q000235:genetics*
D015415:Biomarkers; D002784:Cholesterol; D051546:Cyclooxygenase 2; D003545:Cysteine; D005998:Glycine