Pharmacogenetic interactions between Angiotensin-converting enzyme insertion/deletion polymorphism and response to cibenzoline in patients with hypertrophic obstructive cardiomyopathy.
Cibenzoline, a Class I antiarrhythmic agent, can attenuate the left ventricular pressure gradient (LVPG) in patients with hypertrophic obstructive cardiomyopathy (HOCM). An association between the insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene and the progression of left ventricular hypertrophy in patients with hypertrophic cardiomyopathy has been reported. The aim of this study was to investigate the pharmacogenetic interactions between the ACE insertion/deletion polymorphism and the response to cibenzoline in patients with HOCM. Twenty-four patients with HOCM participated in this study. The LVPG and left ventricular function were measured by echocardiography before and 2 hours after administration of a single oral dose of 200 mg cibenzoline. The ACE insertion/deletion polymorphism was genotyped. The frequencies of the genotypes D/D, D/I, and I/I were 16%, 42%, and 42%, respectively. Before administration of cibenzoline, the LVPG was higher in patients with the D allele than in those without it (105 +/- 47 mm Hg versus 64 +/- 24 mm Hg, P = 0.0195). After administration of cibenzoline, the LVPG significantly decreased to 41 +/- 27 mm Hg in those with the D allele (P = 0.0001) and to 33 +/- 24 mm Hg in those without it (P = 0.0003). The LVPG in patients with the D allele was significantly decreased by cibenzoline when compared with patients without the allele (64 +/- 45 mm Hg versus 31 +/- 17 mm Hg, P = 0.038). Patients with HOCM with the ACE D allele had a high LVPG. Cibenzoline was more effective in patients with HOCM with the ACE D allele.
Ogimoto
Akiyoshi
A
Department of Integrated Medicine and Informatics, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan. aogimoto@m.ehime-u.ac.jp
Okayama
Hideki
H
Nagai
Takayuki
T
Ohtsuka
Tomoaki
T
Suzuki
Jun
J
Inoue
Katsuji
K
Nishimura
Kazuhisa
K
Saito
Makoto
M
Shigematsu
Yuji
Y
Hamada
Mareomi
M
Miki
Tetsuro
T
Higaki
Jitsuo
J
D000284:Administration, Oral; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D002312:Cardiomyopathy, Hypertrophic / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D004247:DNA / Q000235:genetics; D004452:Echocardiography; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D007093:Imidazoles; D004247:DNA; D007703:Peptidyl-Dipeptidase A; C032151:cifenline