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Pharmacogenetic interactions between Angiotensin-converting enzyme insertion/deletion polymorphism and response to

Akiyoshi Ogimoto1, Hideki Okayama, Takayuki Nagai

  • 1Department of Integrated Medicine and Informatics, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan. aogimoto@m.ehime-u.ac.jp

Journal of Cardiovascular Pharmacology
|February 25, 2010
PubMed

Insights

Cibenzoline effectively reduces left ventricular pressure gradient in hypertrophic obstructive cardiomyopathy patients. The angiotensin-converting enzyme D allele is associated with higher pressure gradients and enhanced response to cibenzoline treatment.

Area of Science:

  • Cardiology
  • Pharmacogenetics
  • Genetics

Background:

  • Hypertrophic obstructive cardiomyopathy (HOCM) is characterized by elevated left ventricular pressure gradient (LVPG).
  • The angiotensin-converting enzyme (ACE) insertion/deletion polymorphism is linked to left ventricular hypertrophy progression.
  • Cibenzoline, a Class I antiarrhythmic, can reduce LVPG in HOCM patients.

Purpose of the Study:

  • To investigate pharmacogenetic interactions between ACE insertion/deletion polymorphism and cibenzoline response in HOCM.
  • To determine if ACE genotype influences LVPG and left ventricular function changes after cibenzoline administration.

Main Methods:

  • Twenty-four HOCM patients underwent echocardiography to measure LVPG and left ventricular function.
  • Patients received a single oral dose of 200 mg cibenzoline.
  • ACE insertion/deletion polymorphism was genotyped.

Main Results:

  • Patients with the ACE D allele had significantly higher baseline LVPG compared to those without (105 vs. 64 mm Hg).
  • Cibenzoline significantly reduced LVPG in both groups (D allele: 41 mm Hg; without D allele: 33 mm Hg).
  • The reduction in LVPG by cibenzoline was more pronounced in patients with the ACE D allele (64 vs. 31 mm Hg reduction).

Conclusions:

  • The ACE D allele is associated with higher LVPG in HOCM patients.
  • Cibenzoline demonstrates greater efficacy in reducing LVPG in HOCM patients carrying the ACE D allele.
  • This suggests a pharmacogenetic basis for cibenzoline's effectiveness in HOCM, influenced by ACE genotype.

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