A pharmacogenetic analysis of determinants of hypertension and blood pressure response to angiotensin-converting enzyme inhibitor therapy in patients with vascular disease and healthy individuals
Identifieur interne : 006D86 ( Main/Exploration ); précédent : 006D85; suivant : 006D87A pharmacogenetic analysis of determinants of hypertension and blood pressure response to angiotensin-converting enzyme inhibitor therapy in patients with vascular disease and healthy individuals
Auteurs : Jasper J. Brugts [Pays-Bas] ; Aaron Isaacs [Pays-Bas] ; Moniek P. M. De Maat [Pays-Bas] ; Eric Boersma [Pays-Bas] ; Cock M. Van Duijn [Pays-Bas] ; K. Martijn Akkerhuis [Pays-Bas] ; Andre G. Uitterlinden [Pays-Bas] ; Jacqueline C. M. Witteman [Pays-Bas] ; Francois Cambien [France] ; Claudio Ceconi [Italie] ; Willem Remme [Pays-Bas] ; Michel Bertrand [France] ; Toshiharu Ninomiya [Australie] ; Stephen Harrap [Australie] ; John Chalmers [Australie] ; Stephen Macmahon [Australie] ; Kim Fox [Royaume-Uni] ; Roberto Ferrari [Italie] ; Maarten L. Simoons [Pays-Bas] ; A. H. Jan Danser [Pays-Bas]Source :
- Journal of hypertension [ 0263-6352 ] ; 2011.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
Abstract
Aims To investigate whether genetic variation in the renin- angiotensin-aldosterone system (RAAS) and kallikrein-bradykinin pathways is related to hypertension and blood pressure (BP) response to angiotensin-converting enzyme (ACE) inhibitor therapy in stable coronary artery disease (CAD) patients. Methods and results In 8907 stable CAD patients from the EUROPA trial, 52 haplotype-tagging single-nucleotide polymorphisms (SNPs) in 12 candidate genes within the RAAS and kallikrein-bradykinin pathways were investigated for association with hypertension (defined as BP >160/95 mmHg or use of antihypertensives) and BP response to ACE inhibitors, during a 4-week run-in period. All analyses were adjusted for age, sex, body mass index and creatinine clearance and corrected for multiple testing. Results Hypertension was present in 28.3% of the patients (n = 2526); median BP reduction after perindopril was 10/4 mmHg. Four polymorphisms, located in the ACE (rs4291), angiotensinogen (rs5049) and (pro)renin receptor (rs2968915; rs5981008) genes were significantly associated with hypertension in two vascular disease populations of CAD (EUROPA) and cerebrovascular disease (PROGRESS; n = 3571). A cumulative profile demonstrated a stepwise increase in the prevalence of hypertension, mounting to a 2-3-fold increase (Pfor trend <0.001). Similar associations on hypertension were observed for angiotensinogen in a healthy population (n=2197). In addition, genetic polymorphisms were identified that significantly modified the BP reduction by ACE inhibitor therapy; however, the observed BP differences were small and did not remain significant after permutation analysis. Conclusion This large genetic association study identified genetic determinants of hypertension in three cohorts of patients with vascular disease and healthy individuals.
Affiliations:
- Australie, France, Italie, Pays-Bas, Royaume-Uni
- Angleterre, Grand Londres, Hauts-de-France, Hollande-Méridionale, Nord-Pas-de-Calais, Nouvelle-Galles du Sud, Victoria (État), Île-de-France
- Lille, Londres, Melbourne, Paris, Rotterdam, Sydney
- Université de Melbourne
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Witteman</name><affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Department of Epidemiology & Biostatistics, Erasmus MC</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Cambien, Francois" sort="Cambien, Francois" uniqKey="Cambien F" first="Francois" last="Cambien">Francois Cambien</name><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>INSERM</s1><s2>Paris</s2><s3>FRA</s3><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Ceconi, Claudio" sort="Ceconi, Claudio" uniqKey="Ceconi C" first="Claudio" last="Ceconi">Claudio Ceconi</name><affiliation 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aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region><settlement type="city">Melbourne</settlement></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="Chalmers, John" sort="Chalmers, John" uniqKey="Chalmers J" first="John" last="Chalmers">John Chalmers</name><affiliation wicri:level="3"><inist:fA14 i1="10"><s1>The George Institute, University of Sydney and Royal Prince Alfred Hospital</s1><s2>Sydney</s2><s3>AUS</s3><sZ>13 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Macmahon, Stephen" sort="Macmahon, Stephen" uniqKey="Macmahon S" first="Stephen" last="Macmahon">Stephen Macmahon</name><affiliation wicri:level="3"><inist:fA14 i1="10"><s1>The George Institute, University of Sydney and Royal Prince Alfred Hospital</s1><s2>Sydney</s2><s3>AUS</s3><sZ>13 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Fox, Kim" sort="Fox, Kim" uniqKey="Fox K" first="Kim" last="Fox">Kim Fox</name><affiliation wicri:level="3"><inist:fA14 i1="12"><s1>Royal Brompton and National Heart Institute</s1><s2>London</s2><s3>GBR</s3><sZ>17 aut.</sZ></inist:fA14><country>Royaume-Uni</country><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Ferrari, Roberto" sort="Ferrari, Roberto" uniqKey="Ferrari R" first="Roberto" last="Ferrari">Roberto Ferrari</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>University of Ferrara, and Salvatore Maugeri Foundation, IRCCS</s1><s2>Ferrara</s2><s3>ITA</s3><sZ>10 aut.</sZ><sZ>18 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Ferrara</wicri:noRegion></affiliation></author><author><name sortKey="Simoons, Maarten L" sort="Simoons, Maarten L" uniqKey="Simoons M" first="Maarten L." last="Simoons">Maarten L. Simoons</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Department of Cardiology, Erasmus MC</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Danser, A H Jan" sort="Danser, A H Jan" uniqKey="Danser A" first="A. H. Jan" last="Danser">A. H. Jan Danser</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Department of Internal Medicine, Erasmus MC</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>7 aut.</sZ><sZ>20 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">11-0130883</idno><date when="2011">2011</date><idno type="stanalyst">PASCAL 11-0130883 INIST</idno><idno type="RBID">Pascal:11-0130883</idno><idno type="wicri:Area/PascalFrancis/Corpus">001F69</idno><idno type="wicri:Area/PascalFrancis/Curation">003F66</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">001E05</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">001E05</idno><idno type="wicri:doubleKey">0263-6352:2011:Brugts J:a:pharmacogenetic:analysis</idno><idno type="wicri:Area/Main/Merge">007256</idno><idno type="wicri:Area/Main/Curation">006D86</idno><idno type="wicri:Area/Main/Exploration">006D86</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">A pharmacogenetic analysis of determinants of hypertension and blood pressure response to angiotensin-converting enzyme inhibitor therapy in patients with vascular disease and healthy individuals</title><author><name sortKey="Brugts, Jasper J" sort="Brugts, Jasper J" uniqKey="Brugts J" first="Jasper J." last="Brugts">Jasper J. Brugts</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Department of Cardiology, Erasmus MC</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Isaacs, Aaron" sort="Isaacs, Aaron" uniqKey="Isaacs A" first="Aaron" last="Isaacs">Aaron Isaacs</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Genetic Epidemiology, Erasmus MC</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>2 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="De Maat, Moniek P M" sort="De Maat, Moniek P M" uniqKey="De Maat M" first="Moniek P. M." last="De Maat">Moniek P. M. De Maat</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Department of Haematology, Erasmus MC</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>3 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Boersma, Eric" sort="Boersma, Eric" uniqKey="Boersma E" first="Eric" last="Boersma">Eric Boersma</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Department of Cardiology, Erasmus MC</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Van Duijn, Cock M" sort="Van Duijn, Cock M" uniqKey="Van Duijn C" first="Cock M." last="Van Duijn">Cock M. Van Duijn</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Genetic Epidemiology, Erasmus MC</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>2 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Akkerhuis, K Martijn" sort="Akkerhuis, K Martijn" uniqKey="Akkerhuis K" first="K. Martijn" last="Akkerhuis">K. Martijn Akkerhuis</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Department of Cardiology, Erasmus MC</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Uitterlinden, Andre G" sort="Uitterlinden, Andre G" uniqKey="Uitterlinden A" first="Andre G." last="Uitterlinden">Andre G. Uitterlinden</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Department of Internal Medicine, Erasmus MC</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>7 aut.</sZ><sZ>20 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Department of Epidemiology & Biostatistics, Erasmus MC</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Witteman, Jacqueline C M" sort="Witteman, Jacqueline C M" uniqKey="Witteman J" first="Jacqueline C. M." last="Witteman">Jacqueline C. M. Witteman</name><affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Department of Epidemiology & Biostatistics, Erasmus MC</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Cambien, Francois" sort="Cambien, Francois" uniqKey="Cambien F" first="Francois" last="Cambien">Francois Cambien</name><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>INSERM</s1><s2>Paris</s2><s3>FRA</s3><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Ceconi, Claudio" sort="Ceconi, Claudio" uniqKey="Ceconi C" first="Claudio" last="Ceconi">Claudio Ceconi</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>University of Ferrara, and Salvatore Maugeri Foundation, IRCCS</s1><s2>Ferrara</s2><s3>ITA</s3><sZ>10 aut.</sZ><sZ>18 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Ferrara</wicri:noRegion></affiliation></author><author><name sortKey="Remme, Willem" sort="Remme, Willem" uniqKey="Remme W" first="Willem" last="Remme">Willem Remme</name><affiliation wicri:level="1"><inist:fA14 i1="08"><s1>STICARES Cardiovascular Research</s1><s2>Rhoon</s2><s3>NLD</s3><sZ>11 aut.</sZ></inist:fA14><country>Pays-Bas</country><wicri:noRegion>STICARES Cardiovascular Research</wicri:noRegion></affiliation></author><author><name sortKey="Bertrand, Michel" sort="Bertrand, Michel" uniqKey="Bertrand M" first="Michel" last="Bertrand">Michel Bertrand</name><affiliation wicri:level="3"><inist:fA14 i1="09"><s1>Lille Heart Institute</s1><s2>Lille</s2><s3>FRA</s3><sZ>12 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Ninomiya, Toshiharu" sort="Ninomiya, Toshiharu" uniqKey="Ninomiya T" first="Toshiharu" last="Ninomiya">Toshiharu Ninomiya</name><affiliation wicri:level="3"><inist:fA14 i1="10"><s1>The George Institute, University of Sydney and Royal Prince Alfred Hospital</s1><s2>Sydney</s2><s3>AUS</s3><sZ>13 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Harrap, Stephen" sort="Harrap, Stephen" uniqKey="Harrap S" first="Stephen" last="Harrap">Stephen Harrap</name><affiliation wicri:level="4"><inist:fA14 i1="11"><s1>The University of Melbourne</s1><s2>Melbourne</s2><s3>AUS</s3><sZ>14 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region><settlement type="city">Melbourne</settlement></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="Chalmers, John" sort="Chalmers, John" uniqKey="Chalmers J" first="John" last="Chalmers">John Chalmers</name><affiliation wicri:level="3"><inist:fA14 i1="10"><s1>The George Institute, University of Sydney and Royal Prince Alfred Hospital</s1><s2>Sydney</s2><s3>AUS</s3><sZ>13 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Macmahon, Stephen" sort="Macmahon, Stephen" uniqKey="Macmahon S" first="Stephen" last="Macmahon">Stephen Macmahon</name><affiliation wicri:level="3"><inist:fA14 i1="10"><s1>The George Institute, University of Sydney and Royal Prince Alfred Hospital</s1><s2>Sydney</s2><s3>AUS</s3><sZ>13 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Fox, Kim" sort="Fox, Kim" uniqKey="Fox K" first="Kim" last="Fox">Kim Fox</name><affiliation wicri:level="3"><inist:fA14 i1="12"><s1>Royal Brompton and National Heart Institute</s1><s2>London</s2><s3>GBR</s3><sZ>17 aut.</sZ></inist:fA14><country>Royaume-Uni</country><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Ferrari, Roberto" sort="Ferrari, Roberto" uniqKey="Ferrari R" first="Roberto" last="Ferrari">Roberto Ferrari</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>University of Ferrara, and Salvatore Maugeri Foundation, IRCCS</s1><s2>Ferrara</s2><s3>ITA</s3><sZ>10 aut.</sZ><sZ>18 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Ferrara</wicri:noRegion></affiliation></author><author><name sortKey="Simoons, Maarten L" sort="Simoons, Maarten L" uniqKey="Simoons M" first="Maarten L." last="Simoons">Maarten L. Simoons</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Department of Cardiology, Erasmus MC</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Danser, A H Jan" sort="Danser, A H Jan" uniqKey="Danser A" first="A. H. Jan" last="Danser">A. H. Jan Danser</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Department of Internal Medicine, Erasmus MC</s1><s2>Rotterdam</s2><s3>NLD</s3><sZ>7 aut.</sZ><sZ>20 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author></analytic><series><title level="j" type="main">Journal of hypertension</title><title level="j" type="abbreviated">J. hypertens.</title><idno type="ISSN">0263-6352</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Journal of hypertension</title><title level="j" type="abbreviated">J. hypertens.</title><idno type="ISSN">0263-6352</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>ACE inhibitor</term><term>Aldosterone</term><term>Angiotensin</term><term>Arterial pressure</term><term>Blood pressure</term><term>Cardiovascular disease</term><term>Human</term><term>Hypertension</term><term>Pharmacogenetics</term><term>Polymorphism</term><term>Renin</term><term>Treatment</term><term>Vascular disease</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Hypertension artérielle</term><term>Pathologie des vaisseaux sanguins</term><term>Pathologie de l'appareil circulatoire</term><term>Pharmacogénétique</term><term>Pression artérielle</term><term>Pression sanguine</term><term>Inhibiteur angiotensin converting enzyme</term><term>Traitement</term><term>Homme</term><term>Polymorphisme</term><term>Renin</term><term>Angiotensine</term><term>Aldostérone</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Aims To investigate whether genetic variation in the renin- angiotensin-aldosterone system (RAAS) and kallikrein-bradykinin pathways is related to hypertension and blood pressure (BP) response to angiotensin-converting enzyme (ACE) inhibitor therapy in stable coronary artery disease (CAD) patients. Methods and results In 8907 stable CAD patients from the EUROPA trial, 52 haplotype-tagging single-nucleotide polymorphisms (SNPs) in 12 candidate genes within the RAAS and kallikrein-bradykinin pathways were investigated for association with hypertension (defined as BP >160/95 mmHg or use of antihypertensives) and BP response to ACE inhibitors, during a 4-week run-in period. All analyses were adjusted for age, sex, body mass index and creatinine clearance and corrected for multiple testing. Results Hypertension was present in 28.3% of the patients (n = 2526); median BP reduction after perindopril was 10/4 mmHg. Four polymorphisms, located in the ACE (rs4291), angiotensinogen (rs5049) and (pro)renin receptor (rs2968915; rs5981008) genes were significantly associated with hypertension in two vascular disease populations of CAD (EUROPA) and cerebrovascular disease (PROGRESS; n = 3571). A cumulative profile demonstrated a stepwise increase in the prevalence of hypertension, mounting to a 2-3-fold increase (Pfor trend <0.001). Similar associations on hypertension were observed for angiotensinogen in a healthy population (n=2197). In addition, genetic polymorphisms were identified that significantly modified the BP reduction by ACE inhibitor therapy; however, the observed BP differences were small and did not remain significant after permutation analysis. Conclusion This large genetic association study identified genetic determinants of hypertension in three cohorts of patients with vascular disease and healthy individuals.</div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li><li>Italie</li><li>Pays-Bas</li><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Grand Londres</li><li>Hauts-de-France</li><li>Hollande-Méridionale</li><li>Nord-Pas-de-Calais</li><li>Nouvelle-Galles du Sud</li><li>Victoria (État)</li><li>Île-de-France</li></region><settlement><li>Lille</li><li>Londres</li><li>Melbourne</li><li>Paris</li><li>Rotterdam</li><li>Sydney</li></settlement><orgName><li>Université de Melbourne</li></orgName></list><tree><country name="Pays-Bas"><region name="Hollande-Méridionale"><name sortKey="Brugts, Jasper J" sort="Brugts, Jasper J" uniqKey="Brugts J" first="Jasper J." last="Brugts">Jasper J. Brugts</name></region><name sortKey="Akkerhuis, K Martijn" sort="Akkerhuis, K Martijn" uniqKey="Akkerhuis K" first="K. Martijn" last="Akkerhuis">K. Martijn Akkerhuis</name><name sortKey="Boersma, Eric" sort="Boersma, Eric" uniqKey="Boersma E" first="Eric" last="Boersma">Eric Boersma</name><name sortKey="Danser, A H Jan" sort="Danser, A H Jan" uniqKey="Danser A" first="A. H. Jan" last="Danser">A. H. Jan Danser</name><name sortKey="De Maat, Moniek P M" sort="De Maat, Moniek P M" uniqKey="De Maat M" first="Moniek P. M." last="De Maat">Moniek P. M. De Maat</name><name sortKey="Isaacs, Aaron" sort="Isaacs, Aaron" uniqKey="Isaacs A" first="Aaron" last="Isaacs">Aaron Isaacs</name><name sortKey="Remme, Willem" sort="Remme, Willem" uniqKey="Remme W" first="Willem" last="Remme">Willem Remme</name><name sortKey="Simoons, Maarten L" sort="Simoons, Maarten L" uniqKey="Simoons M" first="Maarten L." last="Simoons">Maarten L. Simoons</name><name sortKey="Uitterlinden, Andre G" sort="Uitterlinden, Andre G" uniqKey="Uitterlinden A" first="Andre G." last="Uitterlinden">Andre G. Uitterlinden</name><name sortKey="Uitterlinden, Andre G" sort="Uitterlinden, Andre G" uniqKey="Uitterlinden A" first="Andre G." last="Uitterlinden">Andre G. Uitterlinden</name><name sortKey="Van Duijn, Cock M" sort="Van Duijn, Cock M" uniqKey="Van Duijn C" first="Cock M." last="Van Duijn">Cock M. Van Duijn</name><name sortKey="Witteman, Jacqueline C M" sort="Witteman, Jacqueline C M" uniqKey="Witteman J" first="Jacqueline C. M." last="Witteman">Jacqueline C. M. Witteman</name></country><country name="France"><region name="Île-de-France"><name sortKey="Cambien, Francois" sort="Cambien, Francois" uniqKey="Cambien F" first="Francois" last="Cambien">Francois Cambien</name></region><name sortKey="Bertrand, Michel" sort="Bertrand, Michel" uniqKey="Bertrand M" first="Michel" last="Bertrand">Michel Bertrand</name></country><country name="Italie"><noRegion><name sortKey="Ceconi, Claudio" sort="Ceconi, Claudio" uniqKey="Ceconi C" first="Claudio" last="Ceconi">Claudio Ceconi</name></noRegion><name sortKey="Ferrari, Roberto" sort="Ferrari, Roberto" uniqKey="Ferrari R" first="Roberto" last="Ferrari">Roberto Ferrari</name></country><country name="Australie"><region name="Nouvelle-Galles du Sud"><name sortKey="Ninomiya, Toshiharu" sort="Ninomiya, Toshiharu" uniqKey="Ninomiya T" first="Toshiharu" last="Ninomiya">Toshiharu Ninomiya</name></region><name sortKey="Chalmers, John" sort="Chalmers, John" uniqKey="Chalmers J" first="John" last="Chalmers">John Chalmers</name><name sortKey="Harrap, Stephen" sort="Harrap, Stephen" uniqKey="Harrap S" first="Stephen" last="Harrap">Stephen Harrap</name><name sortKey="Macmahon, Stephen" sort="Macmahon, Stephen" uniqKey="Macmahon S" first="Stephen" last="Macmahon">Stephen Macmahon</name></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Fox, Kim" sort="Fox, Kim" uniqKey="Fox K" first="Kim" last="Fox">Kim Fox</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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