LTC(4) synthase polymorphism modifies efficacy of botanical seed oil combination in asthma

Botanical seed oils reduce the generation of leukotrienes in patients with asthma. Our objective was to determine the efficacy of a botanical seed oil combination against airflow obstruction in asthma, and to determine the pharmacogenomic effect of the leukotriene C(4) synthase (LTC(4)S) polymorphism A-444C. We conducted a randomized, double-blind, placebo-controlled, cross-over clinical trial in mild to moderate asthmatics to determine the change in FEV(1) after 6 weeks of therapy with borage and echium seed oils versus corn oil placebo. We also examined the effect of the variant LTC(4)S -444C allele on the change in lung function. We did not identify a difference in FEV(1) in the study cohort as a whole (n = 28), nor in the group of A homozygotes. In the C allele carriers (n = 9), FEV(1) improved by 3% after treatment with borage and echium seed oils and declined by 4% after placebo corn oil (p = 0.02). All 9 C allele carriers demonstrated an improvement in their FEV(1) on active treatment compared to placebo as compared to only 7 out of 19 A allele homozygotes (p = 0.007). We observed transient differences in ex vivo leukotriene generation from circulating basophils and granulocytes. We did not observe significant differences in urinary LTE(4) levels. We conclude that compared to corn oil, a combination of borage and echium seed oils improves airflow obstruction in mild to moderate asthmatics who carry the variant allele in the LTC(4)S gene (A-444C). Botanical oil supplementation may have therapeutic potential in asthma if used in a personalized manner. Trial registration: This trial was registered at http://www.clinicaltrials.gov as NCT00806442.