The angiotensin-converting enzyme I/D polymorphism is associated with phagocytic NADPH oxidase-dependent superoxide generation: potential implication in hypertension

Gorka San José , Ana Fortuño , María Ujué Moreno , Pablo Alejandro Robador , Julian Bidegain , Nerea Varo , Oscar Beloqui , Javier Díez , Guillermo Zalba (1)

1 CARDIOVASCULAR SCIENCES

The objective of the present study was to analyse the influence of the angiotensin-converting enzyme (ACE) Insertion/Deletion (I/D) polymorphism on NADPH oxidase-dependent superoxide (•O2-) production, and to deep on the clinical implication of this association in hypertensive patients. A case-control study was performed in a random sample of the general population composed by 189 normotensive subjects and 223 hypertensive patients. ACE polymorphism was determined by PCR. NADPH oxidase-dependent •O2- production was quantified in phagocytic cells by chemiluminescence. Matrix metalloproteinase-9 (MMP-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. I/D polymorphism was not associated with hypertension. NADPH oxidase-dependent •O2- production was significantly higher in DD than in II and ID both in normotensives and hypertensives. Interestingly, plasma levels of angiotensin II were significantly higher in DD than in II and ID both in normotensives and hypertensives. Plasma levels of MMP-9 and systolic blood pressure values were significantly higher in DD than in II and ID in hypertensives, while no differences were found among genotypes in normotensives. Interestingly, NADPH oxidase-dependent •O2- production positively associated with plasma MMP-9 levels in hypertensives, which remained significant after adjustment for age and sex. In conclusion, we reported for the first time an association of the DD genotype of the ACE I/D polymorphism with phagocytic NADPH oxidase-mediated •O2- overproduction. Within the group of hypertensive patients, DD cases also associated with increased blood pressure values and with enhanced plasma levels of MMP-9.

Mots clés: Medicine

Gorka San José, Ana Fortuño, María Ujué Moreno, Pablo Alejandro Robador, Julian Bidegain, et al.. The angiotensin-converting enzyme I/D polymorphism is associated with phagocytic NADPH oxidase-dependent superoxide generation: potential implication in hypertension. Clinical Science, 2009, 116 (3), pp.233-240. ⟨10.1042/CS20080057⟩. ⟨hal-00479427⟩