Predicting the Response to Montelukast by Genetic Variation in Asthmatics

Summary

The purpose of this study is to examine a specific variation in the genetic code for an enzyme (LTC4 synthase) which plays an important role in the airway inflammation associated with asthma. We hypothesize that asthmatic patients with this variant gene will have a better response to montelukast than patients with the wild type gene, as measured by the ability of montelukast to protect against a hypertonic saline challenge.

Timeline

Start

2003-04

Primary completion

—

Completion

2006-12

Publications

• Background Drazen JM, O'Brien J, Sparrow D, Weiss ST, Martins MA, Israel E, Fanta CH. Recovery of leukotriene E4 from the urine of patients with airway obstruction. Am Rev Respir Dis. 1992 Jul;146(1):104-8. doi: 10.1164/ajrccm/146.1.104.
• Background Taylor GW, Taylor I, Black P, Maltby NH, Turner N, Fuller RW, Dollery CT. Urinary leukotriene E4 after antigen challenge and in acute asthma and allergic rhinitis. Lancet. 1989 Mar 18;1(8638):584-8. doi: 10.1016/s0140-6736(89)91611-5.
• Background Drazen JM, Yandava CN, Dube L, Szczerback N, Hippensteel R, Pillari A, Israel E, Schork N, Silverman ES, Katz DA, Drajesk J. Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment. Nat Genet. 1999 Jun;22(2):168-70. doi: 10.1038/9680.
• Background In KH, Asano K, Beier D, Grobholz J, Finn PW, Silverman EK, Silverman ES, Collins T, Fischer AR, Keith TP, Serino K, Kim SW, De Sanctis GT, Yandava C, Pillari A, Rubin P, Kemp J, Israel E, Busse W, Ledford D, Murray JJ, Segal A, Tinkleman D, Drazen JM. Naturally occurring mutations in the human 5-lipoxygenase gene promoter that modify transcription factor binding and reporter gene transcription. J Clin Invest. 1997 Mar 1;99(5):1130-7. doi: 10.1172/JCI119241.
• Background Sanak M, Simon HU, Szczeklik A. Leukotriene C4 synthase promoter polymorphism and risk of aspirin-induced asthma. Lancet. 1997 Nov 29;350(9091):1599-600. doi: 10.1016/s0140-6736(05)64015-9. No abstract available.
• Background Sampson AP, Siddiqui S, Buchanan D, Howarth PH, Holgate ST, Holloway JW, Sayers I. Variant LTC(4) synthase allele modifies cysteinyl leukotriene synthesis in eosinophils and predicts clinical response to zafirlukast. Thorax. 2000 Oct;55 Suppl 2(Suppl 2):S28-31. doi: 10.1136/thorax.55.suppl_2.s28. No abstract available.
• Background Anderson PJ, Garshick E, Blanchard JD, Feldman HA, Brain JD. Intersubject variability in particle deposition does not explain variability in responsiveness to methacholine. Am Rev Respir Dis. 1991 Sep;144(3 Pt 1):649-54. doi: 10.1164/ajrccm/144.3_Pt_1.649.
• Kazani S, Sadeh J, Bunga S, Wechsler ME, Israel E. Cysteinyl leukotriene antagonism inhibits bronchoconstriction in response to hypertonic saline inhalation in asthma. Respir Med. 2011 May;105(5):667-73. doi: 10.1016/j.rmed.2010.11.025. Epub 2010 Dec 18.

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