Studies on the angiotensin converting enzyme gene polymorphism and Ace inhibitors
Chadwick, Ian George
Angiotensin converting enzyme (ACE) converts angiotensin I to angiotensin II, an important step in the control of blood pressure. The gene encoding for ACE is subject to an insertion/deletion (I/D) polymorphism which is associated with different levels of the enzyme in serum. This polymorphism accounts for 47% of the variability in serum ACE concentrations between subjects but its relevance to tissue ACE is unknown. ACE inhibition increases kinin level, for example bradykinin. Kinins have been proposed be involved in the pathogenesis of cough due to ACE inhibitors, a common adverse effect in those prescribed these drugs. A genetic link was proposed to explain the differing susceptibility of subjects to develop cough. Those susceptible may differ in the cough reflexes initially or perhaps have different degrees of tissue ACE activity. In this thesis I examined healthy subjects using substrates and inhibitors of ACE to identify any possible differences in tissue ACE between those of different ACE genotype. I also examined the natural history of ACE inhibitor cough in particular changes in cough reflex and the possible roles of kinins in its aetiology. The frequency of ACE genotype amongst those who developed cough was also examined.