Complement factor H Y402H decreases cardiovascular disease risk in patients with familial hypercholesterolaemia
Aims Activation of the complement system seems an important link between inflammation and atherogenesis. The Y402H polymorphism of complement factor H (CFH) has been associated with cardiovascular events, but results are conflicting and possibly modified by age of onset of cardiovascular disease (CV...
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| Veröffentlicht in: | European heart journal 2009-03, Vol.30 (5), p.618-623 |
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| creator | Koeijvoets, Kristel C.M.C. Mooijaart, Simon P. Dallinga-Thie, Geesje M. Defesche, Joep C. Steyerberg, Ewout W. Westendorp, Rudi G.J. Kastelein, John J.P. van Hagen, P. Martin Sijbrands, Eric J.G. |
| description | Aims Activation of the complement system seems an important link between inflammation and atherogenesis. The Y402H polymorphism of complement factor H (CFH) has been associated with cardiovascular events, but results are conflicting and possibly modified by age of onset of cardiovascular disease (CVD). Methods and results We determined whether or not the Y402H polymorphism influenced CVD risk in a multicentre cohort study involving 2016 unrelated patients with familial hypercholesterolaemia (FH), who have an extremely increased susceptibility to premature CVD. We identified 261 individuals who were homozygous for the polymorphism (CC genotype; 12.9%), 929 individuals who were heterozygous (TC genotype; 46.1%), and 826 individuals carried the wild-type (TT genotype; 41.0%). During 95 115 person years, 644 patients had a cardiovascular event. Carriers of the CC genotype had a decreased risk of CVD (hazard ratio 0.67, 95% confidence interval 0.51–0.87; P = 0.003) relative to the other genotype groups. This association was unaltered after adjustment for clinically relevant cardiovascular risk factors or age effects. Conclusion Among patients with severely increased risk of early onset CVD, the Y402H CFH variant was inversely associated with susceptibility to CVD. This suggests that CFH is a modifier gene of CVD. |
| doi_str_mv | 10.1093/eurheartj/ehn568 |
| format | Article |
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Martin ; Sijbrands, Eric J.G.</creator><creatorcontrib>Koeijvoets, Kristel C.M.C. ; Mooijaart, Simon P. ; Dallinga-Thie, Geesje M. ; Defesche, Joep C. ; Steyerberg, Ewout W. ; Westendorp, Rudi G.J. ; Kastelein, John J.P. ; van Hagen, P. Martin ; Sijbrands, Eric J.G.</creatorcontrib><description>Aims Activation of the complement system seems an important link between inflammation and atherogenesis. The Y402H polymorphism of complement factor H (CFH) has been associated with cardiovascular events, but results are conflicting and possibly modified by age of onset of cardiovascular disease (CVD). Methods and results We determined whether or not the Y402H polymorphism influenced CVD risk in a multicentre cohort study involving 2016 unrelated patients with familial hypercholesterolaemia (FH), who have an extremely increased susceptibility to premature CVD. We identified 261 individuals who were homozygous for the polymorphism (CC genotype; 12.9%), 929 individuals who were heterozygous (TC genotype; 46.1%), and 826 individuals carried the wild-type (TT genotype; 41.0%). During 95 115 person years, 644 patients had a cardiovascular event. Carriers of the CC genotype had a decreased risk of CVD (hazard ratio 0.67, 95% confidence interval 0.51–0.87; P = 0.003) relative to the other genotype groups. This association was unaltered after adjustment for clinically relevant cardiovascular risk factors or age effects. Conclusion Among patients with severely increased risk of early onset CVD, the Y402H CFH variant was inversely associated with susceptibility to CVD. This suggests that CFH is a modifier gene of CVD.</description><identifier>ISSN: 0195-668X</identifier><identifier>EISSN: 1522-9645</identifier><identifier>DOI: 10.1093/eurheartj/ehn568</identifier><identifier>PMID: 19098018</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Adult ; Age Factors ; Atherosclerosis (general aspects, experimental research) ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Cardiovascular disease ; Cardiovascular Diseases - etiology ; Cardiovascular Diseases - genetics ; Complement factor H ; Complement Factor H - genetics ; Disorders of blood lipids. Hyperlipoproteinemia ; Epidemiologic Methods ; Familial hypercholesterolemia ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Hyperlipoproteinemia Type II - complications ; Hyperlipoproteinemia Type II - genetics ; Male ; Medical sciences ; Metabolic diseases ; Middle Aged ; Polymorphism ; Polymorphism, Genetic ; Prognosis</subject><ispartof>European heart journal, 2009-03, Vol.30 (5), p.618-623</ispartof><rights>Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org 2009</rights><rights>2009 INIST-CNRS</rights><rights>Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-1796647e471d6b27ce1a6a7be4a63c06fb2bf1d12d22d36963f704df4b67f9733</citedby><cites>FETCH-LOGICAL-c470t-1796647e471d6b27ce1a6a7be4a63c06fb2bf1d12d22d36963f704df4b67f9733</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,1584,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21257841$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19098018$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Koeijvoets, Kristel C.M.C.</creatorcontrib><creatorcontrib>Mooijaart, Simon P.</creatorcontrib><creatorcontrib>Dallinga-Thie, Geesje M.</creatorcontrib><creatorcontrib>Defesche, Joep C.</creatorcontrib><creatorcontrib>Steyerberg, Ewout W.</creatorcontrib><creatorcontrib>Westendorp, Rudi G.J.</creatorcontrib><creatorcontrib>Kastelein, John J.P.</creatorcontrib><creatorcontrib>van Hagen, P. Martin</creatorcontrib><creatorcontrib>Sijbrands, Eric J.G.</creatorcontrib><title>Complement factor H Y402H decreases cardiovascular disease risk in patients with familial hypercholesterolaemia</title><title>European heart journal</title><addtitle>Eur Heart J</addtitle><description>Aims Activation of the complement system seems an important link between inflammation and atherogenesis. The Y402H polymorphism of complement factor H (CFH) has been associated with cardiovascular events, but results are conflicting and possibly modified by age of onset of cardiovascular disease (CVD). Methods and results We determined whether or not the Y402H polymorphism influenced CVD risk in a multicentre cohort study involving 2016 unrelated patients with familial hypercholesterolaemia (FH), who have an extremely increased susceptibility to premature CVD. We identified 261 individuals who were homozygous for the polymorphism (CC genotype; 12.9%), 929 individuals who were heterozygous (TC genotype; 46.1%), and 826 individuals carried the wild-type (TT genotype; 41.0%). During 95 115 person years, 644 patients had a cardiovascular event. Carriers of the CC genotype had a decreased risk of CVD (hazard ratio 0.67, 95% confidence interval 0.51–0.87; P = 0.003) relative to the other genotype groups. This association was unaltered after adjustment for clinically relevant cardiovascular risk factors or age effects. Conclusion Among patients with severely increased risk of early onset CVD, the Y402H CFH variant was inversely associated with susceptibility to CVD. This suggests that CFH is a modifier gene of CVD.</description><subject>Adult</subject><subject>Age Factors</subject><subject>Atherosclerosis (general aspects, experimental research)</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>Cardiovascular disease</subject><subject>Cardiovascular Diseases - etiology</subject><subject>Cardiovascular Diseases - genetics</subject><subject>Complement factor H</subject><subject>Complement Factor H - genetics</subject><subject>Disorders of blood lipids. Hyperlipoproteinemia</subject><subject>Epidemiologic Methods</subject><subject>Familial hypercholesterolemia</subject><subject>Female</subject><subject>Gene Frequency</subject><subject>Genetic Predisposition to Disease</subject><subject>Genotype</subject><subject>Humans</subject><subject>Hyperlipoproteinemia Type II - complications</subject><subject>Hyperlipoproteinemia Type II - genetics</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metabolic diseases</subject><subject>Middle Aged</subject><subject>Polymorphism</subject><subject>Polymorphism, Genetic</subject><subject>Prognosis</subject><issn>0195-668X</issn><issn>1522-9645</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkcGL1DAUxoMo7rh69yRB0IvUTdI0aY46rI6w6EWXcS4hTV-ZzKZNN2ld9783S4cRPHl68Ph933t8H0IvKXlPiSovYI57MHE6XMB-qET9CK1oxVihBK8eoxWhqiqEqLdn6FlKB0JILah4is6oIqomtF6hsA796KGHYcKdsVOIeIN_csI2uAUbwSRI2JrYuvDLJDt7E3Hr0sMeR5dusBvwaCaX9QnfuWmfXXrnnfF4fz9CtPvgIU0QgzfQO_McPemMT_DiOM_Rj0-X39eb4urb5y_rD1eF5ZJMBZVKCC6BS9qKhkkL1AgjG-BGlJaIrmFNR1vKWsbaUihRdpLwtuONkJ2SZXmO3i6-Ywy3c_5A9y5Z8N4MEOakhVCSslpl8PU_4CHMcci_aUariigieIbIAtkYUorQ6TG63sR7TYl-aEKfmtBLE1ny6ug7Nz20fwXH6DPw5gjkXI3vohmsSyeOUVbJmtPMvVu4MI__c7ZYaJdD_33iTbzRQpay0pvtTm939OvHenetr8s_io60bA</recordid><startdate>20090301</startdate><enddate>20090301</enddate><creator>Koeijvoets, Kristel C.M.C.</creator><creator>Mooijaart, Simon P.</creator><creator>Dallinga-Thie, Geesje M.</creator><creator>Defesche, Joep C.</creator><creator>Steyerberg, Ewout W.</creator><creator>Westendorp, Rudi G.J.</creator><creator>Kastelein, John J.P.</creator><creator>van Hagen, P. Martin</creator><creator>Sijbrands, Eric J.G.</creator><general>Oxford University Press</general><general>Oxford Publishing Limited (England)</general><scope>BSCLL</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>7QP</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>20090301</creationdate><title>Complement factor H Y402H decreases cardiovascular disease risk in patients with familial hypercholesterolaemia</title><author>Koeijvoets, Kristel C.M.C. ; Mooijaart, Simon P. ; Dallinga-Thie, Geesje M. ; Defesche, Joep C. ; Steyerberg, Ewout W. ; Westendorp, Rudi G.J. ; Kastelein, John J.P. ; van Hagen, P. Martin ; Sijbrands, Eric J.G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-1796647e471d6b27ce1a6a7be4a63c06fb2bf1d12d22d36963f704df4b67f9733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adult</topic><topic>Age Factors</topic><topic>Atherosclerosis (general aspects, experimental research)</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Cardiology. Vascular system</topic><topic>Cardiovascular disease</topic><topic>Cardiovascular Diseases - etiology</topic><topic>Cardiovascular Diseases - genetics</topic><topic>Complement factor H</topic><topic>Complement Factor H - genetics</topic><topic>Disorders of blood lipids. Hyperlipoproteinemia</topic><topic>Epidemiologic Methods</topic><topic>Familial hypercholesterolemia</topic><topic>Female</topic><topic>Gene Frequency</topic><topic>Genetic Predisposition to Disease</topic><topic>Genotype</topic><topic>Humans</topic><topic>Hyperlipoproteinemia Type II - complications</topic><topic>Hyperlipoproteinemia Type II - genetics</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metabolic diseases</topic><topic>Middle Aged</topic><topic>Polymorphism</topic><topic>Polymorphism, Genetic</topic><topic>Prognosis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Koeijvoets, Kristel C.M.C.</creatorcontrib><creatorcontrib>Mooijaart, Simon P.</creatorcontrib><creatorcontrib>Dallinga-Thie, Geesje M.</creatorcontrib><creatorcontrib>Defesche, Joep C.</creatorcontrib><creatorcontrib>Steyerberg, Ewout W.</creatorcontrib><creatorcontrib>Westendorp, Rudi G.J.</creatorcontrib><creatorcontrib>Kastelein, John J.P.</creatorcontrib><creatorcontrib>van Hagen, P. Martin</creatorcontrib><creatorcontrib>Sijbrands, Eric J.G.</creatorcontrib><collection>Istex</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>Calcium & Calcified Tissue Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>European heart journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Koeijvoets, Kristel C.M.C.</au><au>Mooijaart, Simon P.</au><au>Dallinga-Thie, Geesje M.</au><au>Defesche, Joep C.</au><au>Steyerberg, Ewout W.</au><au>Westendorp, Rudi G.J.</au><au>Kastelein, John J.P.</au><au>van Hagen, P. Martin</au><au>Sijbrands, Eric J.G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Complement factor H Y402H decreases cardiovascular disease risk in patients with familial hypercholesterolaemia</atitle><jtitle>European heart journal</jtitle><addtitle>Eur Heart J</addtitle><date>2009-03-01</date><risdate>2009</risdate><volume>30</volume><issue>5</issue><spage>618</spage><epage>623</epage><pages>618-623</pages><issn>0195-668X</issn><eissn>1522-9645</eissn><abstract>Aims Activation of the complement system seems an important link between inflammation and atherogenesis. The Y402H polymorphism of complement factor H (CFH) has been associated with cardiovascular events, but results are conflicting and possibly modified by age of onset of cardiovascular disease (CVD). Methods and results We determined whether or not the Y402H polymorphism influenced CVD risk in a multicentre cohort study involving 2016 unrelated patients with familial hypercholesterolaemia (FH), who have an extremely increased susceptibility to premature CVD. We identified 261 individuals who were homozygous for the polymorphism (CC genotype; 12.9%), 929 individuals who were heterozygous (TC genotype; 46.1%), and 826 individuals carried the wild-type (TT genotype; 41.0%). During 95 115 person years, 644 patients had a cardiovascular event. Carriers of the CC genotype had a decreased risk of CVD (hazard ratio 0.67, 95% confidence interval 0.51–0.87; P = 0.003) relative to the other genotype groups. This association was unaltered after adjustment for clinically relevant cardiovascular risk factors or age effects. Conclusion Among patients with severely increased risk of early onset CVD, the Y402H CFH variant was inversely associated with susceptibility to CVD. This suggests that CFH is a modifier gene of CVD.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>19098018</pmid><doi>10.1093/eurheartj/ehn568</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Age Factors Atherosclerosis (general aspects, experimental research) Biological and medical sciences Blood and lymphatic vessels Cardiology. Vascular system Cardiovascular disease Cardiovascular Diseases - etiology Cardiovascular Diseases - genetics Complement factor H Complement Factor H - genetics Disorders of blood lipids. Hyperlipoproteinemia Epidemiologic Methods Familial hypercholesterolemia Female Gene Frequency Genetic Predisposition to Disease Genotype Humans Hyperlipoproteinemia Type II - complications Hyperlipoproteinemia Type II - genetics Male Medical sciences Metabolic diseases Middle Aged Polymorphism Polymorphism, Genetic Prognosis |
| title | Complement factor H Y402H decreases cardiovascular disease risk in patients with familial hypercholesterolaemia |
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