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Common promoter variant in cyclooxygenase-2 represses gene expression - Evidence of role in acute-phase inflammatory response

Papafili, A; Hill, MR; Brull, DJ; McAnulty, RJ; Marshall, RP; Humphries, SE; Laurent, GJ; (2002) Common promoter variant in cyclooxygenase-2 represses gene expression - Evidence of role in acute-phase inflammatory response. ARTERIOSCL THROM VAS , 22 (10) 1631 - 1636. 10.1161/01.ATV.0000030340.80207.C5.

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Abstract

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.

Type:Article
Title:Common promoter variant in cyclooxygenase-2 represses gene expression - Evidence of role in acute-phase inflammatory response
DOI:10.1161/01.ATV.0000030340.80207.C5
Keywords:cyclooxygenase-2, promoter variant, coronary artery bypass graft surgery, C-reactive protein, inflammation, C-REACTIVE PROTEIN, TRANSCRIPTION FACTORS, RHEUMATOID-ARTHRITIS, GEL-ELECTROPHORESIS, PULMONARY-FIBROSIS, SYSTEMIC-SCLEROSIS, LUNG FIBROBLASTS, HEALTHY-MEN, SP-FAMILY, DISEASE
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of) > Internal Medicine
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science

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