The T-786C endothelial nitric oxide synthase genotype is a novel risk factor for coronary artery disease in Caucasian patients of the GENICA study
We investigated the association of polymorphisms in the promoter region and exon 7 endothelial nitric oxide synthase (eNOS) gene with coronary artery disease (CAD). Endothelial dysfunction foretells cardiovascular events and can be genetically determined. We genotyped for the promoter (T-786C) and e...
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| Veröffentlicht in: | Journal of the American College of Cardiology 2003-03, Vol.41 (6), p.930-937 |
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| creator | Paolo Rossi, Gian Cesari, Maurizio Zanchetta, Mario Colonna, Stefania Maiolino, Giuseppe Pedon, Luigi Cavallin, Martina Maiolino, Pietro Pessina, Achille C |
| description | We investigated the association of polymorphisms in the promoter region and exon 7 endothelial nitric oxide synthase (eNOS) gene with coronary artery disease (CAD).
Endothelial dysfunction foretells cardiovascular events and can be genetically determined.
We genotyped for the promoter (T-786C) and exon 7 (Glu298Asp, G894T) polymorphisms in 1,225 subjects; 1,106 were consecutive patients undergoing coronary angiography and 119 control subjects without any cardiovascular risk factors. Genotyping was performed with melting curve analysis of polymerase chain reaction products from allele-specific acceptor and donor probes that were 5′- and 3′-end labeled with LCRed640 and fluorescein, respectively; CAD was assessed by quantitative coronary angiography. We performed multiple logistic regression analysis for the effect of the T-786C, the missense Glu298Asp variant, and other coronary risk factors on two- and three-vessel CAD.
The overall genotype distribution of T-786C (CC = 17.7%, CT = 40.4%, and TT = 41.9%) and Glu298Asp (GG = 43.3%, GT = 37.0%, and TT = 19.7%) was consistent with the Hardy-Weinberg equilibrium. The regression analysis showed that the T-786C, but not the missense Glu298Asp variant, significantly predicted CAD, independent of other risk factors. Compared with TT homozygous, subjects carrying the C allele had a significant (p = 0.002) increase in the odds ratio of harboring two- or three-vessel CAD of 1.672 (95% confidence interval, 1.062 to 2.527). A subgroup analysis confirmed this effect of the T-786C polymorphism in men (p = 0.007), cigarette smokers (p = 0.001), subjects older than 60 years of age (p = 0.007), with hypercholesterolemia (p = 0.011), low high-density lipoprotein cholesterol (p = 0.006), and overweight or with obesity (p = 0.041).
The C allele at the T-786C endothelial nitric oxide synthase polymorphism is associated with a higher risk of multivessel CAD in Caucasians. |
| doi_str_mv | 10.1016/S0735-1097(02)03012-7 |
| format | Article |
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Endothelial dysfunction foretells cardiovascular events and can be genetically determined.
We genotyped for the promoter (T-786C) and exon 7 (Glu298Asp, G894T) polymorphisms in 1,225 subjects; 1,106 were consecutive patients undergoing coronary angiography and 119 control subjects without any cardiovascular risk factors. Genotyping was performed with melting curve analysis of polymerase chain reaction products from allele-specific acceptor and donor probes that were 5′- and 3′-end labeled with LCRed640 and fluorescein, respectively; CAD was assessed by quantitative coronary angiography. We performed multiple logistic regression analysis for the effect of the T-786C, the missense Glu298Asp variant, and other coronary risk factors on two- and three-vessel CAD.
The overall genotype distribution of T-786C (CC = 17.7%, CT = 40.4%, and TT = 41.9%) and Glu298Asp (GG = 43.3%, GT = 37.0%, and TT = 19.7%) was consistent with the Hardy-Weinberg equilibrium. The regression analysis showed that the T-786C, but not the missense Glu298Asp variant, significantly predicted CAD, independent of other risk factors. Compared with TT homozygous, subjects carrying the C allele had a significant (p = 0.002) increase in the odds ratio of harboring two- or three-vessel CAD of 1.672 (95% confidence interval, 1.062 to 2.527). A subgroup analysis confirmed this effect of the T-786C polymorphism in men (p = 0.007), cigarette smokers (p = 0.001), subjects older than 60 years of age (p = 0.007), with hypercholesterolemia (p = 0.011), low high-density lipoprotein cholesterol (p = 0.006), and overweight or with obesity (p = 0.041).
The C allele at the T-786C endothelial nitric oxide synthase polymorphism is associated with a higher risk of multivessel CAD in Caucasians.</description><identifier>ISSN: 0735-1097</identifier><identifier>EISSN: 1558-3597</identifier><identifier>DOI: 10.1016/S0735-1097(02)03012-7</identifier><identifier>PMID: 12651036</identifier><identifier>CODEN: JACCDI</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Adult ; Aged ; Angioplasty ; Biological and medical sciences ; Cardiology ; Cardiology. Vascular system ; Cholesterol ; Coronary Angiography ; Coronary Artery Disease - diagnostic imaging ; Coronary Artery Disease - etiology ; Coronary Artery Disease - genetics ; Coronary heart disease ; Coronary vessels ; European Continental Ancestry Group - genetics ; Exons - genetics ; Female ; Genetic Predisposition to Disease - genetics ; Genotype ; Heart ; Heart attacks ; Humans ; Male ; Medical sciences ; Middle Aged ; Nitric Oxide - genetics ; Nitric Oxide Synthase - genetics ; Polymerase Chain Reaction ; Polymorphism, Genetic - genetics ; Predictive Value of Tests ; Promoter Regions, Genetic - genetics ; Prospective Studies ; Risk Factors ; Severity of Illness Index</subject><ispartof>Journal of the American College of Cardiology, 2003-03, Vol.41 (6), p.930-937</ispartof><rights>2003 American College of Cardiology Foundation</rights><rights>2003 INIST-CNRS</rights><rights>Copyright Elsevier Limited Mar 19, 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c432t-74c97e6912acaca15bcef7e13cb0d318ed4caaf0774ac13eec07039c5ac1ff693</citedby><cites>FETCH-LOGICAL-c432t-74c97e6912acaca15bcef7e13cb0d318ed4caaf0774ac13eec07039c5ac1ff693</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0735-1097(02)03012-7$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14631028$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12651036$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Paolo Rossi, Gian</creatorcontrib><creatorcontrib>Cesari, Maurizio</creatorcontrib><creatorcontrib>Zanchetta, Mario</creatorcontrib><creatorcontrib>Colonna, Stefania</creatorcontrib><creatorcontrib>Maiolino, Giuseppe</creatorcontrib><creatorcontrib>Pedon, Luigi</creatorcontrib><creatorcontrib>Cavallin, Martina</creatorcontrib><creatorcontrib>Maiolino, Pietro</creatorcontrib><creatorcontrib>Pessina, Achille C</creatorcontrib><title>The T-786C endothelial nitric oxide synthase genotype is a novel risk factor for coronary artery disease in Caucasian patients of the GENICA study</title><title>Journal of the American College of Cardiology</title><addtitle>J Am Coll Cardiol</addtitle><description>We investigated the association of polymorphisms in the promoter region and exon 7 endothelial nitric oxide synthase (eNOS) gene with coronary artery disease (CAD).
Endothelial dysfunction foretells cardiovascular events and can be genetically determined.
We genotyped for the promoter (T-786C) and exon 7 (Glu298Asp, G894T) polymorphisms in 1,225 subjects; 1,106 were consecutive patients undergoing coronary angiography and 119 control subjects without any cardiovascular risk factors. Genotyping was performed with melting curve analysis of polymerase chain reaction products from allele-specific acceptor and donor probes that were 5′- and 3′-end labeled with LCRed640 and fluorescein, respectively; CAD was assessed by quantitative coronary angiography. We performed multiple logistic regression analysis for the effect of the T-786C, the missense Glu298Asp variant, and other coronary risk factors on two- and three-vessel CAD.
The overall genotype distribution of T-786C (CC = 17.7%, CT = 40.4%, and TT = 41.9%) and Glu298Asp (GG = 43.3%, GT = 37.0%, and TT = 19.7%) was consistent with the Hardy-Weinberg equilibrium. The regression analysis showed that the T-786C, but not the missense Glu298Asp variant, significantly predicted CAD, independent of other risk factors. Compared with TT homozygous, subjects carrying the C allele had a significant (p = 0.002) increase in the odds ratio of harboring two- or three-vessel CAD of 1.672 (95% confidence interval, 1.062 to 2.527). A subgroup analysis confirmed this effect of the T-786C polymorphism in men (p = 0.007), cigarette smokers (p = 0.001), subjects older than 60 years of age (p = 0.007), with hypercholesterolemia (p = 0.011), low high-density lipoprotein cholesterol (p = 0.006), and overweight or with obesity (p = 0.041).
The C allele at the T-786C endothelial nitric oxide synthase polymorphism is associated with a higher risk of multivessel CAD in Caucasians.</description><subject>Adult</subject><subject>Aged</subject><subject>Angioplasty</subject><subject>Biological and medical sciences</subject><subject>Cardiology</subject><subject>Cardiology. Vascular system</subject><subject>Cholesterol</subject><subject>Coronary Angiography</subject><subject>Coronary Artery Disease - diagnostic imaging</subject><subject>Coronary Artery Disease - etiology</subject><subject>Coronary Artery Disease - genetics</subject><subject>Coronary heart disease</subject><subject>Coronary vessels</subject><subject>European Continental Ancestry Group - genetics</subject><subject>Exons - genetics</subject><subject>Female</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Genotype</subject><subject>Heart</subject><subject>Heart attacks</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Nitric Oxide - genetics</subject><subject>Nitric Oxide Synthase - genetics</subject><subject>Polymerase Chain Reaction</subject><subject>Polymorphism, Genetic - genetics</subject><subject>Predictive Value of Tests</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Prospective Studies</subject><subject>Risk Factors</subject><subject>Severity of Illness Index</subject><issn>0735-1097</issn><issn>1558-3597</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkd-KUzEQxoMobrf6CEpAFL04OjlpknOuRMq6CoteWK9DmjOxWU-TmuQs9jV84k23xQVvZBiGgd_84fsIecbgLQMm330DxUXDoFevoX0DHFjbqAdkxoToGi569ZDM_iJn5DznawCQHesfkzPWSsGAyxn5s9ogXTWqk0uKYYhlg6M3Iw2-JG9p_O0HpHkfysZkpD8wxLLfIfWZGhriDY40-fyTOmNLTNTVtDHFYNKemlSwlsFnPMz6QJdmsiZ7E-jOFI-hZBodrSfp5cWXz8sPNJdp2D8hj5wZMz491Tn5_vFitfzUXH29rNBVYxe8LY1a2F6h7FlrbA0m1hadQsbtGgbOOhwW1hgHSi2MZRzRggLeW1E752TP5-TVce8uxV8T5qK3PlscRxMwTlkrzlqlhKzgi3_A6zilUH_TTIBkXHUdVEocKZtizgmd3iW_rUJoBvpgmb6zTB_80NDqO8vqkTl5fto-rbc43E-dPKrAyxNgsjWjSyZYn--5heQM2q5y748cVtFuPCadbRXZ4uAT2qKH6P_zyi1w2rPu</recordid><startdate>20030319</startdate><enddate>20030319</enddate><creator>Paolo Rossi, Gian</creator><creator>Cesari, Maurizio</creator><creator>Zanchetta, Mario</creator><creator>Colonna, Stefania</creator><creator>Maiolino, Giuseppe</creator><creator>Pedon, Luigi</creator><creator>Cavallin, Martina</creator><creator>Maiolino, Pietro</creator><creator>Pessina, Achille C</creator><general>Elsevier Inc</general><general>Elsevier Science</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</scope><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>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>20030319</creationdate><title>The T-786C endothelial nitric oxide synthase genotype is a novel risk factor for coronary artery disease in Caucasian patients of the GENICA study</title><author>Paolo Rossi, Gian ; Cesari, Maurizio ; Zanchetta, Mario ; Colonna, Stefania ; Maiolino, Giuseppe ; Pedon, Luigi ; Cavallin, Martina ; Maiolino, Pietro ; Pessina, Achille C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c432t-74c97e6912acaca15bcef7e13cb0d318ed4caaf0774ac13eec07039c5ac1ff693</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Angioplasty</topic><topic>Biological and medical sciences</topic><topic>Cardiology</topic><topic>Cardiology. Vascular system</topic><topic>Cholesterol</topic><topic>Coronary Angiography</topic><topic>Coronary Artery Disease - diagnostic imaging</topic><topic>Coronary Artery Disease - etiology</topic><topic>Coronary Artery Disease - genetics</topic><topic>Coronary heart disease</topic><topic>Coronary vessels</topic><topic>European Continental Ancestry Group - genetics</topic><topic>Exons - genetics</topic><topic>Female</topic><topic>Genetic Predisposition to Disease - genetics</topic><topic>Genotype</topic><topic>Heart</topic><topic>Heart attacks</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Nitric Oxide - genetics</topic><topic>Nitric Oxide Synthase - genetics</topic><topic>Polymerase Chain Reaction</topic><topic>Polymorphism, Genetic - genetics</topic><topic>Predictive Value of Tests</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>Prospective Studies</topic><topic>Risk Factors</topic><topic>Severity of Illness Index</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Paolo Rossi, Gian</creatorcontrib><creatorcontrib>Cesari, Maurizio</creatorcontrib><creatorcontrib>Zanchetta, Mario</creatorcontrib><creatorcontrib>Colonna, Stefania</creatorcontrib><creatorcontrib>Maiolino, Giuseppe</creatorcontrib><creatorcontrib>Pedon, Luigi</creatorcontrib><creatorcontrib>Cavallin, Martina</creatorcontrib><creatorcontrib>Maiolino, Pietro</creatorcontrib><creatorcontrib>Pessina, Achille C</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><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>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of the American College of Cardiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Paolo Rossi, Gian</au><au>Cesari, Maurizio</au><au>Zanchetta, Mario</au><au>Colonna, Stefania</au><au>Maiolino, Giuseppe</au><au>Pedon, Luigi</au><au>Cavallin, Martina</au><au>Maiolino, Pietro</au><au>Pessina, Achille C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The T-786C endothelial nitric oxide synthase genotype is a novel risk factor for coronary artery disease in Caucasian patients of the GENICA study</atitle><jtitle>Journal of the American College of Cardiology</jtitle><addtitle>J Am Coll Cardiol</addtitle><date>2003-03-19</date><risdate>2003</risdate><volume>41</volume><issue>6</issue><spage>930</spage><epage>937</epage><pages>930-937</pages><issn>0735-1097</issn><eissn>1558-3597</eissn><coden>JACCDI</coden><abstract>We investigated the association of polymorphisms in the promoter region and exon 7 endothelial nitric oxide synthase (eNOS) gene with coronary artery disease (CAD).
Endothelial dysfunction foretells cardiovascular events and can be genetically determined.
We genotyped for the promoter (T-786C) and exon 7 (Glu298Asp, G894T) polymorphisms in 1,225 subjects; 1,106 were consecutive patients undergoing coronary angiography and 119 control subjects without any cardiovascular risk factors. Genotyping was performed with melting curve analysis of polymerase chain reaction products from allele-specific acceptor and donor probes that were 5′- and 3′-end labeled with LCRed640 and fluorescein, respectively; CAD was assessed by quantitative coronary angiography. We performed multiple logistic regression analysis for the effect of the T-786C, the missense Glu298Asp variant, and other coronary risk factors on two- and three-vessel CAD.
The overall genotype distribution of T-786C (CC = 17.7%, CT = 40.4%, and TT = 41.9%) and Glu298Asp (GG = 43.3%, GT = 37.0%, and TT = 19.7%) was consistent with the Hardy-Weinberg equilibrium. The regression analysis showed that the T-786C, but not the missense Glu298Asp variant, significantly predicted CAD, independent of other risk factors. Compared with TT homozygous, subjects carrying the C allele had a significant (p = 0.002) increase in the odds ratio of harboring two- or three-vessel CAD of 1.672 (95% confidence interval, 1.062 to 2.527). A subgroup analysis confirmed this effect of the T-786C polymorphism in men (p = 0.007), cigarette smokers (p = 0.001), subjects older than 60 years of age (p = 0.007), with hypercholesterolemia (p = 0.011), low high-density lipoprotein cholesterol (p = 0.006), and overweight or with obesity (p = 0.041).
The C allele at the T-786C endothelial nitric oxide synthase polymorphism is associated with a higher risk of multivessel CAD in Caucasians.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>12651036</pmid><doi>10.1016/S0735-1097(02)03012-7</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Angioplasty Biological and medical sciences Cardiology Cardiology. Vascular system Cholesterol Coronary Angiography Coronary Artery Disease - diagnostic imaging Coronary Artery Disease - etiology Coronary Artery Disease - genetics Coronary heart disease Coronary vessels European Continental Ancestry Group - genetics Exons - genetics Female Genetic Predisposition to Disease - genetics Genotype Heart Heart attacks Humans Male Medical sciences Middle Aged Nitric Oxide - genetics Nitric Oxide Synthase - genetics Polymerase Chain Reaction Polymorphism, Genetic - genetics Predictive Value of Tests Promoter Regions, Genetic - genetics Prospective Studies Risk Factors Severity of Illness Index |
| title | The T-786C endothelial nitric oxide synthase genotype is a novel risk factor for coronary artery disease in Caucasian patients of the GENICA study |
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