OBJECTIVE: Cyclooxygenase (COX)-2 is a key regulatory enzyme in the synthesis of prostanoids associated with trauma and inflammation. We investigated the COX-2 gene for functional variants that may influence susceptibility to disease. METHODS AND RESULTS: The promoter of COX-2 was screened for variants in healthy subjects by use of polymerase chain reaction-based methods. Promoter activity was investigated by using reporter expression experiments in human lung fibroblasts. Patients undergoing coronary artery bypass graft surgery, with measurements of plasma markers linked to COX-2 activity, were genotyped for association studies. A common COX-2 promoter variant, -765G>C, was found and shown to be carried by >25% of a group of healthy UK subjects. The -765C allele had significantly lower promoter activity compared with -765G, basally (28+/-3% lower, P<0.005) and in serum-stimulated cells (31+/-2% lower, P<0.005). In patients subjected to coronary artery bypass graft surgery, the magnitude of rise in levels of C-reactive protein (CRP) was strongly genotype dependent. Compared with -765G homozygotes, patients carrying the -765C allele had significantly lower plasma CRP levels at 1 to 4 days after surgery (14% lower at the peak of CRP levels on day 3, P<0.05 for all time points). CONCLUSIONS: For several acute and chronic inflammatory diseases, -765G>C may influence the variability of response observed.


Journal article


Arterioscler Thromb Vasc Biol

Publication Date





1631 - 1636


5' Flanking Region, Acute-Phase Reaction, Alleles, C-Reactive Protein, Cell Line, Coronary Artery Bypass, Coronary Artery Disease, Cyclooxygenase 2, DNA, DNA Mutational Analysis, Gene Expression Regulation, Genetic Predisposition to Disease, Genetic Variation, Genotype, Humans, Isoenzymes, Male, Membrane Proteins, Middle Aged, Peroxidases, Promoter Regions, Genetic, Prostaglandin-Endoperoxide Synthases, Random Allocation, Transfection