Common promoter variant in cyclooxygenase-2 represses gene expression: Evidence of role in acute-phase inflammatory response
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. The promoter of COX-2 was screened for variants in healthy subjects by use o...
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| Veröffentlicht in: | Arteriosclerosis, thrombosis, and vascular biology thrombosis, and vascular biology, 2002-10, Vol.22 (10), p.1631-1636 |
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| container_title | Arteriosclerosis, thrombosis, and vascular biology |
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| creator | PAPAFILI, Anastasia HILL, Michael R BRULL, David J MCANULTY, Robin J MARSHALL, Richard P HUMPHRIES, Steve E LAURENT, Geoffrey J |
| description | 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.
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 |
| doi_str_mv | 10.1161/01.ATV.0000030340.80207.C5 |
| format | Article |
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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).
For several acute and chronic inflammatory diseases, -765G>C may influence the variability of response observed.</description><identifier>ISSN: 1079-5642</identifier><identifier>EISSN: 1524-4636</identifier><identifier>DOI: 10.1161/01.ATV.0000030340.80207.C5</identifier><identifier>PMID: 12377741</identifier><identifier>CODEN: ATVBFA</identifier><language>eng</language><publisher>Philadelphia, PA: Lippincott</publisher><subject>5' Flanking Region - genetics ; Acute-Phase Reaction - genetics ; Alleles ; Biological and medical sciences ; C-Reactive Protein - metabolism ; Cell Line ; Coronary Artery Bypass - methods ; Coronary Artery Disease - blood ; Coronary Artery Disease - surgery ; Cyclooxygenase 2 ; DNA - analysis ; DNA Mutational Analysis ; Gene Expression Regulation - genetics ; Genetic Predisposition to Disease ; Genetic Variation - genetics ; Genetic Variation - physiology ; Genotype ; Humans ; Isoenzymes - genetics ; Isoenzymes - physiology ; Male ; Medical sciences ; Membrane Proteins ; Middle Aged ; Peroxidases - genetics ; Peroxidases - physiology ; Promoter Regions, Genetic - genetics ; Promoter Regions, Genetic - physiology ; Prostaglandin-Endoperoxide Synthases - genetics ; Prostaglandin-Endoperoxide Synthases - physiology ; Random Allocation ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Surgery of the heart ; Transfection</subject><ispartof>Arteriosclerosis, thrombosis, and vascular biology, 2002-10, Vol.22 (10), p.1631-1636</ispartof><rights>2002 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. Oct 2002</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c350t-8ec30147e1ebe11bf59c24ea02da8b89421eb8c84129928cd1c6988861b82ce23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13977987$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12377741$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>PAPAFILI, Anastasia</creatorcontrib><creatorcontrib>HILL, Michael R</creatorcontrib><creatorcontrib>BRULL, David J</creatorcontrib><creatorcontrib>MCANULTY, Robin J</creatorcontrib><creatorcontrib>MARSHALL, Richard P</creatorcontrib><creatorcontrib>HUMPHRIES, Steve E</creatorcontrib><creatorcontrib>LAURENT, Geoffrey J</creatorcontrib><title>Common promoter variant in cyclooxygenase-2 represses gene expression: Evidence of role in acute-phase inflammatory response</title><title>Arteriosclerosis, thrombosis, and vascular biology</title><addtitle>Arterioscler Thromb Vasc Biol</addtitle><description>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.
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).
For several acute and chronic inflammatory diseases, -765G>C may influence the variability of response observed.</description><subject>5' Flanking Region - genetics</subject><subject>Acute-Phase Reaction - genetics</subject><subject>Alleles</subject><subject>Biological and medical sciences</subject><subject>C-Reactive Protein - metabolism</subject><subject>Cell Line</subject><subject>Coronary Artery Bypass - methods</subject><subject>Coronary Artery Disease - blood</subject><subject>Coronary Artery Disease - surgery</subject><subject>Cyclooxygenase 2</subject><subject>DNA - analysis</subject><subject>DNA Mutational Analysis</subject><subject>Gene Expression Regulation - genetics</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic Variation - genetics</subject><subject>Genetic Variation - physiology</subject><subject>Genotype</subject><subject>Humans</subject><subject>Isoenzymes - genetics</subject><subject>Isoenzymes - physiology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Membrane Proteins</subject><subject>Middle Aged</subject><subject>Peroxidases - genetics</subject><subject>Peroxidases - physiology</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Promoter Regions, Genetic - physiology</subject><subject>Prostaglandin-Endoperoxide Synthases - genetics</subject><subject>Prostaglandin-Endoperoxide Synthases - physiology</subject><subject>Random Allocation</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Surgery of the heart</subject><subject>Transfection</subject><issn>1079-5642</issn><issn>1524-4636</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkV9r3SAYh2VsrF23rzCksN0l81UTtXcldH-gsJtut2I8b7aURDNNSg_sw8_THjgwb_TV5_eqPIRcAqsBWvjEoL6--1mzwxBMSFZrxpmqu-YFOYeGy0q2on1Z1kyZqmklPyNvcr4vuOScvSZnwIVSSsI5-dvFeY6BLinOccVEH1waXVjpGKjf-ynGx_0vDC5jxWnCJWHOmGnZQoqPT-UYwxW9eRh3GDzSONAUJzzknd9WrJbfJVzKYXLz7NaY9qVPXmLI-Ja8GtyU8d1xviA_Pt_cdV-r2-9fvnXXt5UXDVsrjV4wkAoBewToh8Z4LtExvnO610bycqC9lsCN4drvwLdGa91Cr7lHLi7Ix-e-5Zd_NsyrncfscZpcwLhlqzgoJrUo4OV_4H3cUihvs5xJwVpmoEBXz5BPMeeEg13SOLu0t8DsQZBlYIsgexJknwTZrinh98cbtn7G3Sl6NFKAD0fAZe-mIbngx3zihFHKaCX-AdkAmuw</recordid><startdate>20021001</startdate><enddate>20021001</enddate><creator>PAPAFILI, Anastasia</creator><creator>HILL, Michael R</creator><creator>BRULL, David J</creator><creator>MCANULTY, Robin J</creator><creator>MARSHALL, Richard P</creator><creator>HUMPHRIES, Steve E</creator><creator>LAURENT, Geoffrey J</creator><general>Lippincott</general><general>American Heart Association, Inc</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>20021001</creationdate><title>Common promoter variant in cyclooxygenase-2 represses gene expression: Evidence of role in acute-phase inflammatory response</title><author>PAPAFILI, Anastasia ; HILL, Michael R ; BRULL, David J ; MCANULTY, Robin J ; MARSHALL, Richard P ; HUMPHRIES, Steve E ; LAURENT, Geoffrey J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c350t-8ec30147e1ebe11bf59c24ea02da8b89421eb8c84129928cd1c6988861b82ce23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>5' Flanking Region - genetics</topic><topic>Acute-Phase Reaction - genetics</topic><topic>Alleles</topic><topic>Biological and medical sciences</topic><topic>C-Reactive Protein - metabolism</topic><topic>Cell Line</topic><topic>Coronary Artery Bypass - methods</topic><topic>Coronary Artery Disease - blood</topic><topic>Coronary Artery Disease - surgery</topic><topic>Cyclooxygenase 2</topic><topic>DNA - analysis</topic><topic>DNA Mutational Analysis</topic><topic>Gene Expression Regulation - genetics</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetic Variation - genetics</topic><topic>Genetic Variation - physiology</topic><topic>Genotype</topic><topic>Humans</topic><topic>Isoenzymes - genetics</topic><topic>Isoenzymes - physiology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Membrane Proteins</topic><topic>Middle Aged</topic><topic>Peroxidases - genetics</topic><topic>Peroxidases - physiology</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>Promoter Regions, Genetic - physiology</topic><topic>Prostaglandin-Endoperoxide Synthases - genetics</topic><topic>Prostaglandin-Endoperoxide Synthases - physiology</topic><topic>Random Allocation</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Surgery of the heart</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>PAPAFILI, Anastasia</creatorcontrib><creatorcontrib>HILL, Michael R</creatorcontrib><creatorcontrib>BRULL, David J</creatorcontrib><creatorcontrib>MCANULTY, Robin J</creatorcontrib><creatorcontrib>MARSHALL, Richard P</creatorcontrib><creatorcontrib>HUMPHRIES, Steve E</creatorcontrib><creatorcontrib>LAURENT, Geoffrey J</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>PAPAFILI, Anastasia</au><au>HILL, Michael R</au><au>BRULL, David J</au><au>MCANULTY, Robin J</au><au>MARSHALL, Richard P</au><au>HUMPHRIES, Steve E</au><au>LAURENT, Geoffrey J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Common promoter variant in cyclooxygenase-2 represses gene expression: Evidence of role in acute-phase inflammatory response</atitle><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle><addtitle>Arterioscler Thromb Vasc Biol</addtitle><date>2002-10-01</date><risdate>2002</risdate><volume>22</volume><issue>10</issue><spage>1631</spage><epage>1636</epage><pages>1631-1636</pages><issn>1079-5642</issn><eissn>1524-4636</eissn><coden>ATVBFA</coden><abstract>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.
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).
For several acute and chronic inflammatory diseases, -765G>C may influence the variability of response observed.</abstract><cop>Philadelphia, PA</cop><cop>Hagerstown, MD</cop><pub>Lippincott</pub><pmid>12377741</pmid><doi>10.1161/01.ATV.0000030340.80207.C5</doi><tpages>6</tpages></addata></record> |
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| identifier | ISSN: 1079-5642 |
| ispartof | Arteriosclerosis, thrombosis, and vascular biology, 2002-10, Vol.22 (10), p.1631-1636 |
| issn | 1079-5642 1524-4636 |
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| subjects | 5' Flanking Region - genetics Acute-Phase Reaction - genetics Alleles Biological and medical sciences C-Reactive Protein - metabolism Cell Line Coronary Artery Bypass - methods Coronary Artery Disease - blood Coronary Artery Disease - surgery Cyclooxygenase 2 DNA - analysis DNA Mutational Analysis Gene Expression Regulation - genetics Genetic Predisposition to Disease Genetic Variation - genetics Genetic Variation - physiology Genotype Humans Isoenzymes - genetics Isoenzymes - physiology Male Medical sciences Membrane Proteins Middle Aged Peroxidases - genetics Peroxidases - physiology Promoter Regions, Genetic - genetics Promoter Regions, Genetic - physiology Prostaglandin-Endoperoxide Synthases - genetics Prostaglandin-Endoperoxide Synthases - physiology Random Allocation Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Surgery of the heart Transfection |
| title | Common promoter variant in cyclooxygenase-2 represses gene expression: Evidence of role in acute-phase inflammatory response |
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