The angiotensin-converting enzyme insertion/deletion polymorphism is associated with phagocytic NADPH oxidase-dependent superoxide generation: potential implication in hypertension
San José G, Fortuño A, Moreno MU, Robador PA, Bidegain J, Varo N [SP], Beloqui O, Díez J, Zalba G.
Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona 31008, Spain.
Magazine: Clinical Science
Date: Feb 1, 2009Biochemistry [SP] Medical Check-Ups Cardiology
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 O(2)(*-) (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 O(2)(*-) 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 O(2)(*-) 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 O(2)(*-) 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 O(2)(*-) 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.
CITATION Clin Sci (Lond). 2009 Feb;116(3):233-40
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