FLAP and the CysLT Receptors

Other candidate genes that may influence patient responses to LT modifier drugs include 5-LO activating protein (FLAP) and the cognate receptors for LTD4, CYSLTR1 and -2. FLAP forms a complex with 5-LO, which facilitates the conversion of arachidonic acid to LTA4 (Fig. 9). Promoter polymorphisms within the FLAP gene (ALOX5AP) promoter have been identified, including a — 336G/A and a CA repeat (47). The cysteinyl-LT receptor 1 (CYSLT1R) gene, which encodes for the receptor that is the major drug target of LTRAs, is also a strong candidate gene. The CYSLT1R gene is located on chromosome Xq13-q26, and a synonymous coding region polymorphism has been described at position 927C/T (48). The regulatory regions controlling the gene expression have only recently been screened for functional polymorphism (Dourodier and Hall, unpublished data), and the potential contribution of this locus to clinical response remains to be established. Because the gene is situated in the unique region of the X chromosome, it is possible that any pharmacogenetic effects resulting from variation at this locus may show sex-specific features.

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