Human ACE gene polymorphism and distilled water induced cough

Area of Science:

• Pharmacogenomics
• Respiratory Medicine
• Cardiovascular Genetics

Background:

• Angiotensin converting enzyme (ACE) inhibitors are known to induce non-productive cough.
• The insertion/deletion (I/D) polymorphism in the ACE gene is a common genetic variation.
• Investigating the ACE genotype's role in cough sensitivity may elucidate mechanisms of ACE inhibitor-induced cough.

Purpose of the Study:

• To determine if the insertion/deletion polymorphism of the angiotensin converting enzyme (ACE) gene is associated with cough sensitivity in healthy individuals.
• To explore the relationship between specific ACE genotypes and the cough reflex.

Main Methods:

• A double-blind, placebo-controlled cough challenge using distilled water aerosols was conducted on 66 normotensive subjects.
• Cough frequency was recorded during a one-minute exposure to water aerosols.
• ACE gene polymorphism (insertion/deletion in intron 16) was analyzed using polymerase chain reaction and agarose gel electrophoresis.

Main Results:

• The study included 66 subjects with genotype distribution: 20 II, 26 ID, and 20 DD.
• A statistically significant relationship (p < 0.01) was observed between ACE genotype and cough response.
• Mean cough counts were 15.8 for II, 11.3 for ID, and 9.6 for DD genotypes, indicating higher cough sensitivity in II individuals.

Conclusions:

• Cough challenge response is significantly dependent on ACE genotype in normal subjects.
• These findings provide evidence for a direct link between angiotensin converting enzyme activity and the cough reflex.
• The ACE I/D polymorphism may influence an individual's susceptibility to cough.