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Proposal 980

Title of the Proposed Research

Association of leukotriene C4 synthase gene (rs730012, -444 A/C) polymorphism with response to leukotriene modifiers treatment in asthma patients

Lead Researcher

Yi-Fan Wu

Affiliation

Institute of Epidemiology and Preventive Medicine
National Taiwan University
Taipei, TW

Funding Source

None

Potential Conflicts of Interest

None

Data Sharing Agreement Date

July 31, 2014

Lay Summary

Asthma, a chronic complex disease of the airways, is characterised by reversible airflow obstruction, bronchial hyper-responsiveness and underlying inflammation. It affects an estimated 300 million people worldwide1. Leukotriene modifiers, one of the three most common controller medications for asthma, can provide clinical benefit in adults and children older than 5 years for symptoms control and pulmonary function improvement.

According to current asthma treatment guidelines (Global Initiative for Asthma, GINA guideline), leukotriene modifiers are recommended as an alternative therapy to low-dose inhaled glucocorticosteroids (ICS) for those with step 2 asthma severity and as an add-on treatment to ICS for those with asthma of step 3 severity.

However, there is significant inter-individual variability in the response to this category of medications.Individual genetic variation about leukotriene biosynthetic pathway may provide a possible explanation for the heterogeneity of treatment effectiveness. Several genetic polymorphisms have been published to be associated with the treatment responsiveness of leukotriene modifiers. I will focus at the polymorphism of the LTC4S (rs730012, -444 A/C) and do a systematic review/ meta-analysis due to it is the mostly discussed in the preliminary literature scoping.

Review objective: To access the association between LTC4S (rs730012, -444 A/C) polymorphism and the treatment effectiveness of leukotriene modifiers in asthma patients.

After performing a systematic review, I think the article (Pharmacogenetics of the 5-lipoxygenase biosynthetic pathway and variable clinical response to montelukast Pharmacogenetics and Genomics 2007, 17:189-196) from the data of SAS40020 and SAS40021 will be helpful for me for the further meta-analysis. We will evaluate the association between LTC4S (-444 A/C) polymorphism and the treatment effectiveness of leukotriene modifiers. According to our knowledge, this is the first review to this issue and may provide a treatment protocol for clinical physicians.

Study Data Provided

Study SAS40020: A Randomized, Double-Blind, Double-Dummy, Parallel Group, 12-Week Comparative Trial of Salmeterol/Fluticasone Propionate Combination Product 50/100mcg BID Via the DISKUS Inhaler Versus Oral Montelukast 10mg QD in Adolescents and Adults with Persistent Asthma
Study SAS40021: A Randomized, Double-Blind, Double-Dummy, Parallel Group, 12-Week Comparative Trial of Salmeterol/Fluticasone Propionate Combination Product 50/100mcg BID Via the DISKUS Inhaler Versus Oral Montelukast 10mg QD in Adolescents and Adults with Persistent Asthma

Statistical Analysis Plan

This will be added after the research is published.

Publication Citation