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. 1997 Feb;52(2):111–113. doi: 10.1136/thx.52.2.111

Human ACE gene polymorphism and distilled water induced cough

A H Morice, A J Turley, T K Linton
PMCID: PMC1758486  PMID: 9059468

Abstract

BACKGROUND: Inhibitors of angiotensin converting enzyme (ACE) cause a non-productive cough. The insertion/deletion polymorphism of ACE was used as a genetic marker to investigate the relationship between ACE genotype and cough sensitivity. METHODS: A double blind cough challenge was performed in 66 normotensive subjects (34 men) of mean age 34.8 years (range 18-80) using aerosols of distilled water. The number of coughs during the one minute exposure to water was recorded. DNA samples from venous blood were amplified by the polymerase chain reaction and resolved on a 1% agarose gel. They were analysed for the presence of a polymorphism in intron 16 of the ACE gene consisting of an insertion (I) or deletion (D) of an Alu repetitive sequence 287 base pairs long. RESULTS: The distribution of genotypes was 20 II, 26 ID, and 20 DD. The cough response was significantly (p < 0.01) related to the ACE genotype, the mean number of coughs being 15.8, 11.3, and 9.6, respectively, in subjects with the II, ID, and DD genotypes. CONCLUSIONS: The observation that cough challenge is dependent on ACE genotype in normal subjects is evidence of a link between ACE activity and the cough reflex. 




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Selected References

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  1. Chadwick I. G., Yeo W. W., Higgins K. S., Jackson P. R., Ramsay L. E., Morice A. H. ACE inhibitors, cough, and genetics. Lancet. 1994 Mar 19;343(8899):740–741. [PubMed] [Google Scholar]
  2. Godden D. J., Borland C., Lowry R., Higenbottam T. W. Chemical specificity of coughing in man. Clin Sci (Lond) 1986 Mar;70(3):301–306. doi: 10.1042/cs0700301. [DOI] [PubMed] [Google Scholar]
  3. Hubert C., Houot A. M., Corvol P., Soubrier F. Structure of the angiotensin I-converting enzyme gene. Two alternate promoters correspond to evolutionary steps of a duplicated gene. J Biol Chem. 1991 Aug 15;266(23):15377–15383. [PubMed] [Google Scholar]
  4. Joris L., Dab I., Quinton P. M. Elemental composition of human airway surface fluid in healthy and diseased airways. Am Rev Respir Dis. 1993 Dec;148(6 Pt 1):1633–1637. doi: 10.1164/ajrccm/148.6_Pt_1.1633. [DOI] [PubMed] [Google Scholar]
  5. Morice A. H., Higgins K. S., Yeo W. W. Adaptation of cough reflex with different types of stimulation. Eur Respir J. 1992 Jul;5(7):841–847. [PubMed] [Google Scholar]
  6. Morice A. H., Lowry R., Brown M. J., Higenbottam T. Angiotensin-converting enzyme and the cough reflex. Lancet. 1987 Nov 14;2(8568):1116–1118. doi: 10.1016/s0140-6736(87)91547-9. [DOI] [PubMed] [Google Scholar]
  7. Rigat B., Hubert C., Alhenc-Gelas F., Cambien F., Corvol P., Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest. 1990 Oct;86(4):1343–1346. doi: 10.1172/JCI114844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Rigat B., Hubert C., Corvol P., Soubrier F. PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene (DCP1) (dipeptidyl carboxypeptidase 1). Nucleic Acids Res. 1992 Mar 25;20(6):1433–1433. doi: 10.1093/nar/20.6.1433-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Sesoko S., Kaneko Y. Cough associated with the use of captopril. Arch Intern Med. 1985 Aug;145(8):1524–1524. [PubMed] [Google Scholar]
  10. Soubrier F., Hubert C., Testut P., Nadaud S., Alhenc-Gelas F., Corvol P. Molecular biology of the angiotensin I converting enzyme: I. Biochemistry and structure of the gene. J Hypertens. 1993 May;11(5):471–476. doi: 10.1097/00004872-199305000-00001. [DOI] [PubMed] [Google Scholar]
  11. Tomaki M., Ichinose M., Miura M., Hirayama Y., Kageyama N., Yamauchi H., Shirato K. Angiotensin converting enzyme (ACE) inhibitor-induced cough and substance P. Thorax. 1996 Feb;51(2):199–201. doi: 10.1136/thx.51.2.199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ujiie Y., Sekizawa K., Aikawa T., Sasaki H. Evidence for substance P as an endogenous substance causing cough in guinea pigs. Am Rev Respir Dis. 1993 Dec;148(6 Pt 1):1628–1632. doi: 10.1164/ajrccm/148.6_Pt_1.1628. [DOI] [PubMed] [Google Scholar]
  13. Yeo W. W., Ramsay L. E., Morice A. H. ACE inhibitor cough: a genetic link? Lancet. 1991 Jan 19;337(8734):187–187. doi: 10.1016/0140-6736(91)90861-i. [DOI] [PubMed] [Google Scholar]
  14. Yeo W. W., Ramsay L. E. Persistent dry cough with enalapril: incidence depends on method used. J Hum Hypertens. 1990 Oct;4(5):517–520. [PubMed] [Google Scholar]

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