Key result
In hypertensive patients with atrial fibrillation, the ACE D allele was associated with attenuated type-I collagen degradation (p=0.011), whereas ACE inhibitor therapy increased degradation (p=0.036).
Why the study?
Does ACE I/D genotype and ACE inhibitor therapy affect collagen type I synthesis and degradation markers in hypertensive patients with atrial fibrillation?
Observational (n=332)
Does ACE I/D genotype and ACE inhibitor therapy affect collagen type I synthesis and degradation markers in hypertensive patients with atrial fibrillation?
The ACE D allele is associated with reduced collagen type I degradation in hypertensive patients with AF, while ACE inhibitor therapy increases degradation, suggesting a pharmacogenetic interaction.
Should not yet alter ACE inhibitor use by genotype in hypertensive AF; hypothesis-generating for pharmacogenetic effects on fibrosis.
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.
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Tziakas et al. (2007) conducted an observational in Atrial fibrillation and arterial hypertension (n=332). ACE insertion/deletion genotype and ACE inhibitors vs. I/I carriers vs D allele carriers; no ACE inhibitors was evaluated on Serum concentrations of amino-terminal propeptide of pro-collagen type I (PINP) and carboxy-terminal telopeptide of collagen type I (CITP) (p=0.011). In hypertensive patients with atrial fibrillation, the ACE D allele was associated with attenuated type-I collagen degradation (p=0.011), whereas ACE inhibitor therapy increased degradation (p=0.036).
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