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Genetic polymorphisms of 5-LO

  • Chapter
Novel Inhibitors of Leukotrienes

Part of the book series: Progress in Inflammation Research ((PIR))

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Abstract

The clinical success of zileuton and other 5-lipoxygenase (5-LO) inhibitors for the treatment of asthma strongly supports the hypothesis that alterations in the expression of 5-LO have important implications in the pathogenesis of diseases characterized by excess leukotriene production. In a clinical trial with zileuton about 50% of patients have shown a sustained improvement in FEV1 (force expiratory volume at 1 sec) of ≥ 10% in response to 5-LO inhibition [1]. It is likely that the issues of incomplete therapeutic responses in asthma are not isolated to 5-LO inhibitors perse, but are problems associated with all antiasthmatic drugs, and reflect the fact that asthma is a heterogeneous disease with complex and interdependent genetic and environmental etiologic factors [2, 3]. One intriguing possibility is that the leukocytes of asthmatics differ in their functional expression of 5-LO, such that 5-LO products contribute to a variable extent in the overall pathogenesis of asthma. As a result of these differences, patients overexpressing 5-LO, and therefore 5-LO products, will be more responsive to 5-LO inhibition, whereas other patients whose disease is less dependent on 5-LO activity will be less responsive to these drugs. Is there a potential for genetic differences in the 5-LO gene to be responsible for altered 5-LO expression and some of the observed heterogeneity among asthmatic patients? The answer to this question appears to be yes, and because of its essential role in the formation of leukotrienes, 5-LO is considered to be an excellent candidate gene in the ongoing search for genetic polymorphisms that may account for asthma development or phenotypic variability. This chapter will review what is known about 5-LO gene regulation and how this regulation may be altered by naturally occurring promoter mutations.

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Author information

Authors and Affiliations

  1. Pulmonary and Critical Care Division, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA

    Eric S. Silverman, Kwang H. In & Jeffrey M. Drazen

  2. Vascular Research Division, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA

    Eric S. Silverman & Tucker Collins

Authors
  1. Eric S. Silverman
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  2. Kwang H. In
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  3. Tucker Collins
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  4. Jeffrey M. Drazen
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Editor information

Editors and Affiliations

  1. Center for Cardiopulmonary Pharmacology Institute of Pharmacological Sciences, University of Milan, Via Balzaretti 9, Milan, 20133, Italy

    Giancarlo Folco

  2. Department of Medical Biochemistry and Biophysics Division of Physiological Chemistry II, Karolinska Institute, Stockholm, 10401, Sweden

    Bengt Samuelsson

  3. National Jewish Medical and Research Center, 1400 Jackson St., Denver, CO, 80206, USA

    Robert C. Murphy

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© 1999 Springer Basel AG

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Silverman, E.S., In, K.H., Collins, T., Drazen, J.M. (1999). Genetic polymorphisms of 5-LO. In: Folco, G., Samuelsson, B., Murphy, R.C. (eds) Novel Inhibitors of Leukotrienes. Progress in Inflammation Research. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8703-8_10

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  • DOI: https://doi.org/10.1007/978-3-0348-8703-8_10

  • Publisher Name: Birkhäuser, Basel

  • Print ISBN: 978-3-0348-9736-5

  • Online ISBN: 978-3-0348-8703-8

  • eBook Packages: Springer Book Archive

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