{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:50:57Z","timestamp":1790470257310,"version":"4.1.0"},"reference-count":40,"publisher":"Portland Press Ltd.","issue":"3","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,2,1]]},"abstract":"<jats:p>The objective of the present study was to analyse the influence of the ACE (angiotensin-converting enzyme) gene I\/D (insertion\/deletion) polymorphism on NADPH oxidase-dependent O2\u2022\u2212 (superoxide radical) production, and to investigate the clinical implication of this association in hypertensive subjects. A case-control study was performed in a random sample of the general population composed of 189 normotensive subjects and 223 hypertensive subjects. The ACE polymorphism was determined by PCR. NADPH oxidase-dependent O2\u2022\u2212 production was quantified in phagocytic cells by chemiluminescence. MMP-9 (matrix metalloproteinase-9), a marker of atherosclerosis previously reported to be associated with NADPH oxidase overactivity, was quantified by ELISA in plasma samples. The distribution of genotypes was in Hardy\u2013Weinberg equilibrium. The I\/D polymorphism was not associated with hypertension. NADPH oxidase-dependent O2\u2022\u2212 production was significantly higher in D\/D (deletion\/deletion) than in I\/I (insertion\/insertion) and I\/D, both in normotensive and hypertensive subjects. Interestingly, plasma levels of angiotensin II were significantly higher in D\/D than in I\/I and I\/D, both in normotensive and hypertensive subjects. Plasma levels of MMP-9 and systolic blood pressure values were significantly higher in D\/D than in I\/I and I\/D hypertensive subjects, whereas no differences were found among genotypes in normotensive subjects. Interestingly, NADPH oxidase-dependent O2\u2022\u2212 production positively associated with plasma MMP-9 levels in hypertensive subjects, which remained significant after adjustment for age and gender. In conclusion, in the present study we have reported for the first time an association of the D\/D genotype of the ACE I\/D polymorphism with phagocytic NADPH oxidase-mediated O2\u2022\u2212 overproduction. Within the group of hypertensive patients, D\/D cases also associated with increased blood pressure values and with enhanced plasma levels of MMP-9.<\/jats:p>","DOI":"10.1042\/cs20080057","type":"journal-article","created":{"date-parts":[[2008,7,23]],"date-time":"2008-07-23T09:51:36Z","timestamp":1216806696000},"page":"233-240","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The angiotensin-converting enzyme insertion\/deletion polymorphism is associated with phagocytic NADPH oxidase-dependent superoxide generation: potential implication in hypertension"],"prefix":"10.1042","volume":"116","author":[{"given":"Gorka","family":"San\u00a0Jos\u00e9","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona 31008, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Fortu\u00f1o","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona 31008, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda\u00a0U.","family":"Moreno","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona 31008, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo\u00a0A.","family":"Robador","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona 31008, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julen","family":"Bidegain","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona 31008, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nerea","family":"Varo","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona 31008, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Beloqui","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University Clinic, University of Navarra, Pamplona 31008, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"D\u00edez","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona 31008, Spain"},{"name":"Department of Cardiology and Cardiovascular Surgery, University Clinic, University of Navarra, Pamplona 31008, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"Zalba","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona 31008, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2009,1,8]]},"reference":[{"key":"2021113010114671600_B1","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1161\/01.RES.0000223145.74217.e7","article-title":"ACE polymorphisms","volume":"98","author":"Sayed-Tabatabaei","year":"2006","journal-title":"Circ. 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