The COX-2 G/C -765 polymorphism may modulate the occurrence of cerebrovascular ischemia.
In the atherosclerotic plaque, cyclooxygenase-2 (COX-2) catalyzes prostaglandin E formation, which acts as a pro-atherogenic factor. A polymorphism, G/C -765, within the COX-2 promoter region modulates gene expression and the risk of cerebrovascular disease. We have evaluated the relation between COX-2 G/C -765 genotypes and the occurrence of cerebrovascular ischemia. We evaluated the COX-2 G/C -765 polymorphism in 110 consecutive patients with a documented history of acute ischemic cerebrovascular disease, in 110 age-matched and sex-matched subjects without such history, and in a general population (n = 324) from the same ethnical background. The frequency of the COX-2 -765C allele in patients [0.21; 95% confidence interval (CI), 0.16-0.26] was similar to those found in controls (0.28; 95% CI, 0.22-0.34) and in the general population (0.26; 95% CI, 0.23-0.29). Carriers of the CC genotype differed between patients (0.02; 95% CI, 0.00-0.05) and controls [0.10 (95% CI, 0.04-0.16), P = 0.019; odds ratio, 0.17 (95% CI, 0.04-0.79)] or the general population [0.08 (95% CI, 0.05-0.11), P = 0.023; odds ratio, 0.22 (95% CI, 0.05-0.95)]. In a multiple logistic regression analysis adjusted for confounding variables, smoking status (P < 0.001), atrial fibrillation (P = 0.004) and COX-2 G/C-765 polymorphism (P = 0.016) independently contributed to cerebrovascular ischemia, with CC carriers exhibiting a lower risk (odds ratio, 0.07; 95% CI, 0.01-0.61). Our data show an association between the COX-2 G/C-765 gene polymorphism and cerebrovascular ischemia, suggesting that the COX-2 gene is a susceptibility locus for the risk of cerebrovascular ischemic disease.
Unita' di Aterosclerosi e Trombosi, I.R.C.C.S. Casa Sollievo della Sofferenza, S. Giovanni Rotondo, Italy.
Donatella
D
Colaizzo
Laura
L
Fofi
Gianluca
G
Tiscia
Renzo
R
Guglielmi
Nicola
N
Cocomazzi
Massimiliano
M
Prencipe
Maurizio
M
Margaglione
Danilo
D
Toni
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D050197:Atherosclerosis / Q000201:enzymology / Q000235:genetics; D001281:Atrial Fibrillation / Q000201:enzymology / Q000235:genetics; D002545:Brain Ischemia / Q000201:enzymology / Q000235:genetics*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics; D012307:Risk Factors
D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human