Angiotensin converting enzyme insertion/deletion polymorphism and the risk of heart failure in hypertensive subjects

• Published in: European heart journal Vol. 25; no. 23; pp. 2143 - 2148
• Main Authors: Schut, Anna F.C., Bleumink, Gysèle S., Stricker, Bruno H.Ch, Hofman, Albert, Witteman, Jacqueline C.M., Pols, Huibert A.P., Deckers, Jaap W., Deinum, Jaap, van Duijn, Cornelia M.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.12.2004
• Subjects: Aged; Alleles; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure - genetics; Cardiology. Vascular system; Chromosome aberrations; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; DNA Transposable Elements - genetics; Epidemiologic Methods; Female; Genotype; Heart; Heart Failure - genetics; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Humans; Hypertension - genetics; Male; Medical genetics; Medical sciences; Middle Aged; Peptidyl-Dipeptidase A - genetics; Polymerase Chain Reaction - methods; Polymorphism, Genetic; Sequence Deletion; Human; Hypertension; Heart failure; ACE; Enzyme; Insertion; Cardiovascular disease; Risk; Peptidases; Peptidyl-dipeptidase A; Heart disease; Risk factor; Deletion; Hydrolases; Peptidyl-dipeptidases; Genetics; Polymorphism
• ISSN: 0195-668X; 1522-9645
• DOI: 10.1016/j.ehj.2004.08.026

Aims Cardiac angiotensin-I converting enzyme (ACE) activity is influenced by the ACE I/D polymorphism. Evidence suggests that the DD-genotype may be a risk factor for cardiac hypertrophy and heart failure, especially in hypertensive subjects. We assessed the relation between the ACE I/D polymorphism and the risk of incident heart failure in normotensive and hypertensive subjects. Methods and results We investigated 4264 normotensive and 2174 hypertensive participants of the Rotterdam Study, a population based prospective cohort study. All subjects were available for follow-up from 1990 until 2000. Incidence rates (IR) of heart failure in normotensive subjects were the same over all genotype strata (10 per 1000 person-years). In hypertensive subjects, the IR increased with the number of D-alleles present (II: IR=13, ID: IR=18 and DD: IR=20 per 1000 person-years). Hypertensive subjects carrying the II-genotype did not have an increased risk of heart failure compared to normotensive II subjects. However, hypertensive subjects carrying one or two copies of the D-allele did have a significantly increased risk of heart failure (ID: RR: 1.4 (1.1–1.9) and DD: RR: 1.5 (1.2–2.1)). Conclusion Our findings suggest that the ACE I/D polymorphism may play a modifying role in the development of heart failure in hypertensive subjects.