LTC4 synthase polymorphism modifies efficacy of botanical seed oil combination in asthma.
LTC4 synthase polymorphism modifies efficacy of botanical seed oil combination in asthma.
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DOI：
10.1186/2193-1801-3-661
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Israel E
中科院分区：
文献类型：
--
作者：
Kazani S;Arm JP;Boyce J;Chhay H;Dutile S;Wechsler ME;Govindarajulu U;Ivester P;Ainsworth HC;Sergeant S;Chilton FH;Israel E
植物种子油可减少哮喘患者白三烯的生成。我们的目的是确定一种植物种子油组合对哮喘气流阻塞的疗效，并确定白三烯C4合成酶(LTC4S)基因多态性A-444c的药物基因组效应。我们在轻中度哮喘患者中进行了一项随机、双盲、安慰剂对照的交叉临床试验，以确定在6周的治疗后，用萝卜油和湿疹籽油与玉米油安慰剂治疗后FEV1的变化。我们还检测了LTC4S-444c变异等位基因对肺功能改变的影响。我们没有发现FEV1在整个研究队列中的差异(n=28)，也没有在A纯合子组中发现差异。在C等位基因携带者(n=9)中，FEV1在用萝卜油和石榴籽油治疗后改善3%，在安慰剂玉米油治疗后下降4%(p=0.02)。与安慰剂相比，所有9个C等位基因携带者在积极治疗后FEV1均有改善，而19个A等位基因纯合子中只有7个改善了FEV1(p=0.007)。我们观察到体外循环中的嗜碱性粒细胞和粒细胞产生白三烯的瞬时差异。我们没有观察到尿LTE4水平的显著差异。我们的结论是，与玉米油相比，萝卜油和洋葱籽油的组合改善了携带LTC4S基因变异等位基因(A-444c)的轻中度哮喘患者的气流阻塞。如果以个性化的方式使用，植物油补充剂可能对哮喘具有治疗潜力。试验注册：这项试验在http://www.clinicaltrials.gov注册为NCT00806442。
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. Trial registration: This trial was registered at http://www.clinicaltrials.gov as NCT00806442.
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影响因子：
14.2
作者：
Tantisira, Kelan G.;Drazen, Jeffrey M.
通讯作者：
Drazen, Jeffrey M.
DOI：
10.1056/nejmoa0911353
发表时间：
2011-09-29
期刊：
The New England journal of medicine
影响因子：
--
作者：
Tantisira KG;Lasky-Su J;Harada M;Murphy A;Litonjua AA;Himes BE;Lange C;Lazarus R;Sylvia J;Klanderman B;Duan QL;Qiu W;Hirota T;Martinez FD;Mauger D;Sorkness C;Szefler S;Lazarus SC;Lemanske RF Jr;Peters SP;Lima JJ;Nakamura Y;Tamari M;Weiss ST
通讯作者：
Weiss ST
影响因子：
4.3
作者：
Barnes, N;Wei, LX;Edelman, JM
通讯作者：
Edelman, JM
影响因子：
10
作者：
Sayers, I;Barton, S;Holgate, ST
通讯作者：
Holgate, ST
影响因子：
24.3
作者：
Nagakura, T;Matsuda, S;Hata, K
通讯作者：
Hata, K