title: Pharmacogenomics of Prostaglandin and Leukotriene Receptors.
abstract: Individual genetic background together with environmental effects are thought to be behind many human complex diseases. A number of genetic variants, mainly single nucleotide polymorphisms (SNPs), have been shown to be associated with various pathological and inflammatory conditions, representing potential therapeutic targets. Prostaglandins (PTGs) and leukotrienes (LTs) are eicosanoids derived from arachidonic acid and related polyunsaturated fatty acids that participate in both normal homeostasis and inflammatory conditions. These bioactive lipid mediators are synthesized through two major multistep enzymatic pathways: PTGs by cyclooxygenase and LTs by 5-lipoxygenase. The main physiological effects of PTGs include vasodilation and vascular leakage (PTGE2); mast cell maturation, eosinophil recruitment, and allergic responses (PTGD2); vascular and respiratory smooth muscle contraction (PTGF2), and inhibition of platelet aggregation (PTGI2). LTB4 is mainly involved in neutrophil recruitment, vascular leakage, and epithelial barrier function, whereas cysteinyl LTs (CysLTs) (LTC4, LTD4, and LTE4) induce bronchoconstriction and neutrophil extravasation, and also participate in vascular leakage. PTGs and LTs exert their biological functions by binding to cognate receptors, which belong to the seven transmembrane, G protein-coupled receptor superfamily. SNPs in genes encoding these receptors may influence their functionality and have a role in disease susceptibility and drug treatment response. In this review we summarize SNPs in PTGs and LTs receptors and their relevance in human diseases. We also provide information on gene expression. Finally, we speculate on future directions for this topic.
authors.affiliation: Research Laboratory, International Business Information Management Association (IBIMA)-Regional University Hospital of Malaga, University of Málaga (UMA)Malaga, Spain; Allergy Unit, International Business Information Management Association (IBIMA)-Regional University Hospital of Malaga, University of Málaga (UMA)Malaga, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Cornejo-García
authors.affiliation: Research Laboratory, International Business Information Management Association (IBIMA)-Regional University Hospital of Malaga, University of Málaga (UMA) Malaga, Spain.
authors.forename: James R
authors.initials: JR
authors.lastname: Perkins
authors.affiliation: Research Laboratory, International Business Information Management Association (IBIMA)-Regional University Hospital of Malaga, University of Málaga (UMA) Malaga, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Jurado-Escobar
authors.affiliation: Department of Pharmacology, University of Extremadura Caceres, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: García-Martín
authors.affiliation: Department of Pharmacology, University of Extremadura Caceres, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Agúndez
authors.affiliation: Genetics Unit, Department of Cell Biology, Genetics and Physiology, Faculty of Sciences, University of Málaga Malaga, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Viguera
authors.affiliation: Allergy Unit, International Business Information Management Association (IBIMA)-Regional University Hospital of Malaga, University of Málaga (UMA) Malaga, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: Pérez-Sánchez
authors.affiliation: Allergy Service, Infanta Leonor University Hospital Madrid, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: Blanca-López
keywords: NSAID-hypersensitivity; eicosanoid receptors polymorphisms; inflammation; leukotrienes; prostaglandins