title: LTC4 synthase polymorphism modifies efficacy of botanical seed oil combination in asthma.
abstract: 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 C4 synthase (LTC4S) 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 FEV1 after 6 weeks of therapy with borage and echium seed oils versus corn oil placebo. We also examined the effect of the variant LTC4S -444C allele on the change in lung function. We did not identify a difference in FEV1 in the study cohort as a whole (n = 28), nor in the group of A homozygotes. In the C allele carriers (n = 9), FEV1 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 FEV1 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 LTE4 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 LTC4S gene (A-444C). Botanical oil supplementation may have therapeutic potential in asthma if used in a personalized manner.
  
  
  BACKGROUND
  This trial was registered at http://www.clinicaltrials.gov as NCT00806442.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115 USA.
authors.forename: Shamsah
authors.initials: S
authors.lastname: Kazani
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA USA.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Arm
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Boyce
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA USA.
authors.forename: Heng
authors.initials: H
authors.lastname: Chhay
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115 USA.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dutile
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115 USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Wechsler
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA USA.
authors.forename: Usha
authors.initials: U
authors.lastname: Govindarajulu
authors.affiliation: Departments of Physiology/Pharmacology, Wake Forest University Health Sciences, Winston-Salem, NC USA ; Wake Forest University Center for Botanical Lipids and Inflammatory Disease Prevention, Wake Forest University Health Sciences, Winston-Salem, NC USA.
authors.forename: Priscilla
authors.initials: P
authors.lastname: Ivester
authors.affiliation: Departments of Physiology/Pharmacology, Wake Forest University Health Sciences, Winston-Salem, NC USA ; Wake Forest University Center for Botanical Lipids and Inflammatory Disease Prevention, Wake Forest University Health Sciences, Winston-Salem, NC USA.
authors.forename: Hannah C
authors.initials: HC
authors.lastname: Ainsworth
authors.affiliation: Departments of Biochemistry, Wake Forest University Health Sciences, Winston-Salem, NC USA ; Wake Forest University Center for Botanical Lipids and Inflammatory Disease Prevention, Wake Forest University Health Sciences, Winston-Salem, NC USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Sergeant
authors.affiliation: Departments of Physiology/Pharmacology, Wake Forest University Health Sciences, Winston-Salem, NC USA ; Wake Forest University Center for Botanical Lipids and Inflammatory Disease Prevention, Wake Forest University Health Sciences, Winston-Salem, NC USA.
authors.forename: Floyd H
authors.initials: FH
authors.lastname: Chilton
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115 USA.
authors.forename: Elliot
authors.initials: E
authors.lastname: Israel
keywords: Asthma; Borage oil; Echium oil; LTC4 synthase; Leukotrienes