Angiotensin-converting enzyme-gene polymorphism is associated with collagen I synthesis and QT dispersion in essential hypertension.
OBJECTIVE
This study tested the hypothesis that abnormal QT dispersion, an indicator of arrhythmogenic risk, is associated with angiotensin-converting enzyme (ACE) gene polymorphism and abnormalities of collagen metabolism.


METHODS
A total of 132 patients with untreated essential hypertension (EHT) were recruited. QT dispersion corrected by heart rate (QTc) on a 12-lead electrocardiogram, ACE genotype, left ventricular mass index (LVMI) and E/A ratio using echocardiogram, plasma ACE activity and serum propeptide type I C-terminal procollagen (PICP) concentration, a marker of myocardial fibrosis, were determined. A normal control group (NC) of 200 normotensive subjects was used for comparison of QT dispersion.


RESULTS
Number of EHT patients with ACE genotype I/I, I/D and D/D was 61, 52 and 19, respectively. LVMI and E/A ratio were similar in the three groups. Compared with subjects with I/I or I/D genotype, subjects with D/D showed higher plasma ACE activity (I/I: 13 +/- 0.6, I/D: 17 +/- 0.9, and D/D: 21 +/- 1.1 nmol/min per ml, mean +/- SE, P05) and serum PICP concentration (I/I: 106 +/- 5.4, I/D: 106 +/- 4.9, D/D: 140 +/- 12.1 ng/ml, P < 0.01). QTc dispersion was larger in the three hypertensive subgroups than in NC, and was the largest in EHT with D/D (NC: 0.037 +/- 0.001, I/I: 0.056 +/- 0.003, I/D: 0.055 +/- 0.002, D/D: 0.069 +/- 0.004 s, P < 0.05).


CONCLUSIONS
ACE D/D genotype could be associated with an elevation of serum PICP concentration possibly leading to myocardial fibrosis and increased QT dispersion.
Takahashi
Toru
T
Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan.
Ueno
Hitoshi
H
Yasumoto
Kotaro
K
Kagitani
Satoshi
S
Tomoda
Fumihiro
F
Inoue
Hiroshi
H
Takata
Masanobu
M
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000235:genetics; D004562:Electrocardiography; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006329:Heart Conduction System / Q000378:metabolism / Q000503:physiopathology; D006339:Heart Rate / Q000235:genetics; D006352:Heart Ventricles / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000097:blood / Q000235:genetics / Q000503:physiopathology; D007564:Japan; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D007703:Peptidyl-Dipeptidase A / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics*; D011347:Procollagen / Q000097:blood; D013223:Statistics as Topic
D015415:Biomarkers; D010446:Peptide Fragments; D011347:Procollagen; C042813:procollagen type I carboxy terminal peptide; D007703:Peptidyl-Dipeptidase A