Response to angiotensin-converting enzyme inhibition is selectively blunted by high sodium in angiotensin-converting enzyme DD genotype:Evidence for gene-environment interaction in healthy volunteers

Background Renin-angiotensin-aldosterone system blockade is a cornerstone in cardiovascular protection. Angiotensin-converting enzyme (ACE)-DD genotype has been associated with resistance to angiotensin-converting enzyme inhibition (ACEi), but data are conflicting. As sodium intake modifies the effect of ACEi as well as the genotype-phenotype relationship, we hypothesize gene-environment interaction between sodium-status, the response to ACEi, and ACE genotype.Method Thirty-five male volunteers (26 +/- 9 years; II n=6, ID n=18, DD n=11) were studied during placebo and ACEi (double blind, enalapril 20mg/day) on low [7 days 50 mmol Na+/day (low salt)] and high[7 days 200 mmol Na+/day (high salt)] sodium, with a washout of 6 weeks in-between. After each period mean arterial pressure (MAP) was measured before and during graded infusion of angiotensin II (Ang II).Results During high salt, ACEi reduced MAP in II and ID, but not in DD [II: 88 (78-94) versus 76 (72-88); ID: 87 (84-91) versus 83 (79-87); both PConclusion In healthy participants, the MAP response to ACEi is selectively blunted in DD genotype during high salt, accompanied by blunted sensitivity to Ang II. Low salt corrects both abnormalities. Further analysis of this gene-environment interaction in patients may contribute to strategies for improvement of individual treatment efficacy. J Hypertens 28:2414-2421 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.