From Pharmacogenomics to Improved Patient Outcomes: Angiotensin I-Converting Enzyme as an Example

Abstract

Here we report the utility of a molecular epidemiologic approach for common, polygenic diseases. Since 1992, the angiotensin I-converting enzyme (ACE) deletion/deletion (D/D) genotype has been linked to several cardiovascular diseases, including diabetic nephropathy. Earlier, the ACE D/D genotype had been associated with excess tissue ACE activity. We have observed an association of the ACE D/D genotype with a large number of common diseases, including chronic renal failure due to non-insulin-dependent diabetes mellitus or hypertension, hypertensive peripheral vascular disease, and emphysema [chronic obstructive pulmonary disease (COPD)]. ACE inhibitors have been in clinical use since 1977 and have a well-known safety record. Armed with the knowledge that ACE overactivity was associated with their disease, we gave what was intended to be a tissue ACE-inhibitory dose of a hydrophobic ACE inhibitor to 800 Caucasian and African-American male patients with hypertension and 200 Caucasian and African-American male patients with chronic renal failure, over a period of 3 years. We here report their outcomes, which include those of two patients with end-stage hypertensive peripheral vascular disease and one patient with end-stage emphysema (COPD). As a group, the outcomes are superior to what is available in the literature. This experience suggests the power of pharmacogenomics to improve clinical outcomes for common diseases safely, quickly, and inexpensively, if effective drugs already exist.