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•− (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•− 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–Weinberg equilibrium. The I/D polymorphism was not associated with hypertension. NADPH oxidase-dependent O2•− 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•− 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•− 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.
Skip Nav Destination
Article navigation
February 2009
-
Cover Image
Cover Image
- PDF Icon PDF LinkTable of Contents
Research Article|
January 08 2009
The angiotensin-converting enzyme insertion/deletion polymorphism is associated with phagocytic NADPH oxidase-dependent superoxide generation: potential implication in hypertension
Gorka San José;
Gorka San José
*Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona 31008, Spain
Search for other works by this author on:
Ana Fortuño;
Ana Fortuño
*Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona 31008, Spain
Search for other works by this author on:
María U. Moreno;
María U. Moreno
*Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona 31008, Spain
Search for other works by this author on:
Pablo A. Robador;
Pablo A. Robador
*Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona 31008, Spain
Search for other works by this author on:
Julen Bidegain;
Julen Bidegain
*Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona 31008, Spain
Search for other works by this author on:
Nerea Varo;
Nerea Varo
*Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona 31008, Spain
Search for other works by this author on:
Oscar Beloqui;
Oscar Beloqui
†Department of Internal Medicine, University Clinic, University of Navarra, Pamplona 31008, Spain
Search for other works by this author on:
Javier Díez;
Javier Díez
*Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona 31008, Spain
‡Department of Cardiology and Cardiovascular Surgery, University Clinic, University of Navarra, Pamplona 31008, Spain
Search for other works by this author on:
Guillermo Zalba
*Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona 31008, Spain
Correspondence: Dr Guillermo Zalba (email gzalba@unav.es).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
February 20 2008
Revision Received:
June 27 2008
Accepted:
July 22 2008
Accepted Manuscript online:
July 22 2008
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2009 Biochemical Society
2009
Clin Sci (Lond) (2009) 116 (3): 233–240.
Article history
Received:
February 20 2008
Revision Received:
June 27 2008
Accepted:
July 22 2008
Accepted Manuscript online:
July 22 2008
Connected Content
Citation
Gorka San José, Ana Fortuño, María U. Moreno, Pablo A. Robador, Julen Bidegain, Nerea Varo, Oscar Beloqui, Javier Díez, Guillermo Zalba; The angiotensin-converting enzyme insertion/deletion polymorphism is associated with phagocytic NADPH oxidase-dependent superoxide generation: potential implication in hypertension. Clin Sci (Lond) 1 February 2009; 116 (3): 233–240. doi: https://doi.org/10.1042/CS20080057
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.