Pharmacogenetics of asthma

Abstract

Recent advances in the extent of knowledge regarding interindividual genetic variation in drug treatment targets and drug metabolizing enzymes has resulted in studies designed to assess the contribution of genetic variability to treatment response in a range of diseases. This review describes the current state of knowledge of genetic variability in key airway targets important in the treatment of asthma. Whilst the genes coding for some key treatment targets contain little polymorphic variation (e.g. the muscarinic M2 and M3 receptors) other genes whose products are important targets in the treatment of asthma contain extensive genetic variation. The best examples of the latter are the beta2-adrenoceptor and the 5-lipoxygenase genes. Genetic variability in both of these genes may account in part for interindividual variability in treatment response. Finally, a number of key targets within the airways remain to be adequately screened for polymorphic variation.

Figure 1

β₂-adrenoceptor polymorphisms. Degenerate substitutions are shown in black. (Reproduced with permission from Liggett [19]).

Figure 2

The lipoxygenase pathway of leukotriene synthesis. HPETE: hydroperoxyeicosatetraenoic acid; LT: leukotriene; 5-LOX: 5-lipoxygenase; FLAP: 5-lipoxygenase activating protein; LTC4S: leukotriene C4 synthase.