title: Pharmacogenetic interactions between Angiotensin-converting enzyme insertion/deletion polymorphism and response to cibenzoline in patients with hypertrophic obstructive cardiomyopathy.
abstract: 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.
authors.affiliation: Department of Integrated Medicine and Informatics, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan. aogimoto@m.ehime-u.ac.jp
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Ogimoto
authors.forename: Hideki
authors.initials: H
authors.lastname: Okayama
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nagai
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Ohtsuka
authors.forename: Jun
authors.initials: J
authors.lastname: Suzuki
authors.forename: Katsuji
authors.initials: K
authors.lastname: Inoue
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Nishimura
authors.forename: Makoto
authors.initials: M
authors.lastname: Saito
authors.forename: Yuji
authors.initials: Y
authors.lastname: Shigematsu
authors.forename: Mareomi
authors.initials: M
authors.lastname: Hamada
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Miki
authors.forename: Jitsuo
authors.initials: J
authors.lastname: Higaki
mesh_terms: 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
chemical_list: D000889:Anti-Arrhythmia Agents; D007093:Imidazoles; D004247:DNA; D007703:Peptidyl-Dipeptidase A; C032151:cifenline