Effect of angiotensin-converting enzyme insertion/deletion genotype on collagen type I synthesis and degradation in patients with atrial fibrillation and arterial hypertension.

Objective: The present study was undertaken to assess the impact of the angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphisms on circulating markers of collagen type I synthesis and degradation, and also to study the effect of therapy with ACE inhibitors on these markers in hypertensive patients with atrial fibrillation (AF).

Research Design And Methods: ACE I/D genotypes were assessed in 158 hypertensive patients (71 +/- 9 years; 72 male) with AF and 174 patients with arterial hypertension in sinus rhythm (SR) (71 +/- 9 years; 88 male). Serum concentrations of amino-terminal propeptide of pro-collagen type I (PINP) and of carboxy-terminal telopeptide of collagen type I (CITP), indices of collagen type I synthesis and degradation, respectively, were measured.

Results: Of the 332 study participants, 74 (22.3%) were I/I, 158 (47.6%) were I/D and 100 (30.1%) were D/D carriers. Genetic variation in ACE significantly influenced serum CITP levels in AF patients (p = 0.011). CITP levels were lower in D allele carriers (DD and ID) compared with I/I carriers. There was no difference in PINP levels between the different ACE genotype groups (p = 0.302). Patients treated with ACE inhibitors had higher CITP levels compared with those not treated (p = 0.036).

Conclusions: This study suggests that the presence of the D allele in hypertensive patients with AF is associated with attenuation of type-I collagen degradation, and that therapy with ACE inhibitors increases degradation of collagen type I. The data indicate a subgroup of patients with AF and arterial hypertension who may benefit to a greater extent from therapy with ACE inhibitors, thus, providing a basis for pharmacogenetics.