Arachidonate 5-lipoxygenase promoter genotype, dietary arachidonic acid, and atherosclerosis.
Arachidonate 5-lipoxygenase promoter genotype, dietary arachidonic acid, and atherosclerosis.
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DOI：
10.1016/j.jvs.2004.03.014
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发表时间：
2004-06
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影响因子：
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通讯作者：
J. Dwyer;H. Allayee;K. Dwyer;Jingxu Fan;Huiyun Wu;R. Mar;A. Lusis;M. Mehrabian
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文献类型：
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作者：
J. Dwyer;H. Allayee;K. Dwyer;Jingxu Fan;Huiyun Wu;R. Mar;A. Lusis;M. Mehrabian
研究背景白三烯是由花生四烯酸（多不饱和n-6脂肪酸）经5-脂氧合酶作用产生的炎症介质。由于动脉粥样硬化涉及动脉炎症，我们假设5-脂氧合酶基因启动子的多态性可能与人类动脉粥样硬化有关，并且这种效应可能与竞争性5-脂氧合酶底物的饮食摄入相互作用。来自洛杉矶动脉粥样硬化研究的中年男女。饮食花生四烯酸和海洋n-3脂肪酸（包括竞争5-脂氧合酶底物，减少炎症性白三烯的产生）进行了测量，使用6个24小时的回忆的食物intake.ResultsVariant 5-lipoxygenase基因型（缺乏共同的等位基因）被发现在6.0%的队列。与普通（野生型）等位基因携带者相比，两种变异等位基因携带者的平均（±SE）内膜-中膜厚度（经年龄、性别、身高和种族或民族校正）增加了80±19 μm（95%置信区间，43 ~ 116; P<0.001）。在多变量分析中，两个变异等位基因携带者的内膜中层厚度增加（62 μm，P<0.001）与糖尿病（64 μm，P=0.01）相似，糖尿病是最常见的心血管危险因素。增加膳食花生四烯酸显著增强基因型的表观致动脉粥样硬化作用，而增加膳食摄入的n-3脂肪酸钝化的效果。最后，血浆中的C-反应蛋白，炎症的标志物，增加了一个因素2之间的两个变异等位基因的载体相比，在载体之间的共同allele.Conclusionsvariant 5-lipoxygenase基因型确定一个亚群动脉粥样硬化增加。观察到的饮食基因相互作用进一步表明，饮食n-6多不饱和脂肪酸促进，而海洋n-3脂肪酸抑制，白三烯介导的炎症，导致动脉粥样硬化在这个亚群。
BackgroundLeukotrienes are inflammatory mediators generated from arachidonic acid (polyunsaturated n–6 fatty acid) by the enzyme 5-lipoxygenase. Since atherosclerosis involves arterial inflammation, we hypothesized that a polymorphism in the 5-lipoxygenase gene promoter could relate to atherosclerosis in humans and that this effect could interact with the dietary intake of competing 5-lipoxygenase substrates.MethodsWe determined 5-lipoxygenase genotypes, carotid-artery intima–media thickness, and markers of inflammation in a randomly sampled cohort of 470 healthy, middle-aged women and men from the Los Angeles Atherosclerosis Study. Dietary arachidonic acid and marine n–3 fatty acids (including a competing 5-lipoxygenase substrate that reduces the production of inflammatory leukotrienes) were measured with the use of six 24-hour recalls of food intake.ResultsVariant 5-lipoxygenase genotypes (lacking the common allele) were found in 6.0 percent of the cohort. Mean (±SE) intima–media thickness adjusted for age, sex, height, and racial or ethnic group was increased by 80±19 μm (95 percent confidence interval, 43 to 116; P<0.001) among carriers of two variant alleles, as compared with carriers of the common (wild-type) allele. In multivariate analysis, the increase in intima–media thickness among carriers of two variant alleles (62 μm, P<0.001) was similar in this cohort to that associated with diabetes (64 μm, P=0.01), the strongest common cardiovascular risk factor. Increased dietary arachidonic acid significantly enhanced the apparent atherogenic effect of genotype, whereas increased dietary intake of n–3 fatty acids blunted the effect. Finally, the plasma level of C-reactive protein, a marker of inflammation, was increased by a factor of 2 among carriers of two variant alleles as compared with that among carriers of the common allele.ConclusionsVariant 5-lipoxygenase genotypes identify a subpopulation with increased atherosclerosis. The observed diet–gene interactions further suggest that dietary n–6 polyunsaturated fatty acids promote, whereas marine n–3 fatty acids inhibit, leukotriene-mediated inflammation that leads to atherosclerosis in this subpopulation.