Common Promoter Variant in Cyclooxygenase-2 Represses Gene Expression
| Autor: | DJ Brull, Robin J. McAnulty, Richard P. Marshall, Geoffrey J. Laurent, Michael Hill, Steve E. Humphries, Anastasia Papafili |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Male
medicine.medical_specialty Pathology Genotype 5' Flanking Region DNA Mutational Analysis Inflammation Coronary Artery Disease Biology Transfection Cell Line Pathogenesis Random Allocation Internal medicine Gene expression medicine Humans Genetic Predisposition to Disease Coronary Artery Bypass Allele Acute-Phase Reaction Promoter Regions Genetic Gene Alleles C-reactive protein Genetic Variation Membrane Proteins DNA Middle Aged Isoenzymes C-Reactive Protein Endocrinology Gene Expression Regulation Peroxidases Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases biology.protein Cyclooxygenase medicine.symptom Cardiology and Cardiovascular Medicine |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 22:1631-1636 |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/01.atv.0000030340.80207.c5 |
| Popis: | 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 P P Conclusions— For several acute and chronic inflammatory diseases, −765G>C may influence the variability of response observed. |
| Databáze: | OpenAIRE |
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