Rapid communication Human ACE gene polymorphism and distilled water induced cough

to an Alu repetitive sequence 287 base pairs (bp) long has been described. The ACE inBackground – Inhibitors of angiotensin converting enzyme (ACE) cause a nonsertion/deletion polymorphism was found to be associated with serum levels of ACE and, in productive cough. The insertion/deletion polymorphism of ACE was used as a gensubjects who are homozygous for the D allele, the mean serum level of ACE is nearly twice etic marker to investigate the relationship between ACE genotype and cough sensias high as that of subjects homozygous for the I allele. tivity. Methods – A double blind cough challenge Since the introduction of ACE inhibitors for the treatment of hypertension and heart failure was performed in 66 normotensive subjects (34 men) of mean age 34.8 years in the late 1970s their use has grown steadily. However, it was not until 1985 that the as(range 18–80) using aerosols of distilled water. The number of coughs during the sociation of ACE inhibitors with a dry cough was noted. This side effect of ACE inhibitors one minute exposure to water was recorded. DNA samples from venous blood appears to be related to the class of the drug rather than to individual compounds as it has were amplified by the polymerase chain reaction and resolved on a 1% agarose gel. been reported with all ACE inhibitors in current use. They were analysed for the presence of a polymorphism in intron 16 of the ACE ACE inhibitors have been shown to cause a leftward shift in the concentration-response gene consisting of an insertion (I) or deletion (D) of an Alu repetitive sequence curve for the tussive agent capsaicin, and it has been postulated that inhibition of ACE leads 287 base pairs long. Results – The distribution of genotypes to accumulation of protussive peptides such as bradykinin and substance P which cause the was 20 II, 26 ID, and 20 DD. The cough response was significantly (p<0.01) related heightened cough response. Despite much research, the biochemical mechanism of ACE to the ACE genotype, the mean number of coughs being 15.8, 11.3, and 9.6, reinhibitor cough remains to be elucidated. Following the discovery of a genetic polyspectively, in subjects with the II, ID, and DD genotypes. morphism within the ACE gene, we suggested a relationship between the polymorphism and Conclusions – The observation that cough challenge is dependent on ACE genotype the cough reflex. However, a simple relationship between ACE genotype and ACE in normal subjects is evidence of a link between ACE activity and the cough reflex. inhibitor cough does not exist. In this study we have postulated that the response to cough (Thorax 1997;52:111–113) evoked by distilled water may be related to the ACE gene polymorphism with subjects of