Clinical Characteristics and Angiotensin Converting Enzyme Gene Polymorphism in the Susceptibility to Angiotensin Converting Enzyme Inhibitor-Induced Cough

Lee, Sang Chol; Kim, Hyo Soo; Choi, Jin Ho; Choi, Hyun Seok; Park, Dae Gyun; Sohn, Dae Won; Oh, Byung Hee; Lee, Myoung Mook; Park, Young Bae; Seo, Jung Don; Choi, Yun Shik; Lee, Young Woo

Abstract

BACKGROUND
Cough is a frequent side effect of angiotensin converting enzyme(ACE) inhibitors and the mechanism of cough is postulated to be associated with accumulation of bronchial irritants which are substrates of ACE. Based on this pathophysiologic mechanism, baseline ACE activity could potentially play the key role in the development of ACE inhibitor-induced cough and ACE gene polymorphism, which account for part of the ACE activity, and to compare the clinical characteristics between subjects who developed cough and those who did not with ACE inhibitor use. METHOD: The cough group(N=84) consisted of subjects who developed troublesome cough with ACE inhibiors and who ceased coughing in 4 weeks after cessation of ACE inhibitor treatment. Patients with evidence of acute respiratioy illness were excluded. The non-cough group(N=116) consisted of subjects who did not develop cough with over 12 months of ACE inhibitor treatment. Clinical characteristics were collected by personal contact and chart review. ACE genotyping was done by PCR amplification of DNA from peripheral blood using previously published primers and agarose gel electrophoresis.
RESULTS
Underlying diseases of the cough group were hypertension(47), valvular heart disease(23), ischemic heart disease(4), dilated cardiomyopathy(7) and others (3), whereas Underlying diseases of the non-cough group were hypertension(48), valvular heart disease(33), ischemic heart disease(12), dilated cardiomyopathy(20) and others(3). There was no significant difference in the distribution of underlying diseases between the two groups. Cough induced by ACE inhibitors occurred in an average of 8 weeks after treatment initiation and subsided in an average of 3.8 weeks after discontinuation of ACE inhibitors. There was a preponderance of females in the cough group(F : M=73 : 27) compared to the non-cough group(F : M=40 : 60, p<0.01). There was no significant difference in mean age, total cholesterol, and the frequency of hypertension and diabetes between the two groups. Genotypic frequencies of ACE gene were I/I : I/D : D/D=38 : 42 : 30 for the cough group and 45 : 36 : 19 for the non-cough group which showed no significant difference between the two groups. Allelic frequencies were I : D=54 : 46 and 62 : 38 in the cough and non-cough group respectively and the difference was not statistically significant.
CONCLUSION
Women are more susceptible to ACE inhibitor-induced cough, and ACE inhibitor induced cough is not associated with ACE gene polymorphism.