Cys Leukotriene Receptor Pathway Polymorphism

With the increasing use of Cys leukotriene (LT1) receptor antagonists, such as montelu-kast, and the realization that not all individuals respond to this class of drugs, there has been considerable attention paid to the possibility that genetic factors may contribute to response to this class of drugs and also to other drugs active in leukotriene synthesis pathways, most notably 5-lipoxygenase (LO) inhibitors.

LTs are important mediators of airway narrowing in asthma. Their actions are mediated through two receptors, CLTR1 and CLTR2: Of these, CLTR1 is the major airway receptor and is responsible for mediating bronchoconstrictor effects. CLTR1 antagonists have been developed for the treatment of asthma, including montelukast and zafir-lukast, and in addition there are leukotriene synthesis inhibitors, such as zileuton, which have also shown some clinical efficacy in trials. There are a number of regulatory steps, which control the expression of LTs in airway tissue and which are potentially subject to regulation at the genetic level, that might therefore be of pharmacogenetic interest. These are summarized in the following.

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