Nutrigenetic association of the 5-lipoxygenase gene with myocardial infarction
Nutrigenetic association of the 5-lipoxygenase gene with myocardial infarction
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DOI：
10.1093/ajcn/88.4.934
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发表时间：
2008-10-01
影响因子：
7.1
通讯作者：
Campos, Hannia
中科院分区：
文献类型：
--
作者：
Allayee, Hooman;Baylin, Ana;Campos, Hannia
背景资料：5-脂氧合酶（5-LO）催化花生四烯酸（AA）生物合成促炎性白三烯的限速步骤，并与动物模型和人类的动脉粥样硬化有关。我们先前报道了5-LO启动子重复多态性的变异体与人类颈动脉粥样硬化相关，这种影响被高饮食AA加剧，但被高饮食n-3脂肪酸减轻。目的：我们试图用更临床相关的表型如心肌梗死（MI）来证实这些初步观察结果。设计：在1885例哥斯达黎加病例对照组中对5-LO多态性进行基因分型，并检测其与MI的相关性。进行功能实验，以确定相关的等位基因是否有差异的mRNA expression.Results：变异基因型组的频率没有显着差异病例组和对照组。然而，观察到一个显著的基因x饮食相互作用，其中，相对于常见的5重复等位基因，3和4等位基因在高饮食AA组（>= 0.25 g/d）中与较高的MI风险相关（比值比：1.31; 95% CI：1.07，1.61），而在低饮食AA组（>= 0.25 g/d）中与较低的MI风险相关（比值比：1.31; 95% CI：1.07，1.61）。
Background: 5-Lipoxygenase (5-LO) catalyzes the rate-limiting step of the biosynthesis of proinflammatory leukotrienes from arachidonic acid (AA) and has been associated with atherosclerosis in animal models and humans. We previously reported that variants of a 5-LO promoter repeat polymorphism were associated with carotid atherosclerosis in humans, an effect that was exacerbated by high dietary AA but mitigated by high dietary n-3 fatty acids.Objective: We sought to confirm these initial observations with a more clinically relevant phenotype such as myocardial infarction (MI).Design: The 5-LO polymorphism was genotyped in 1885 Costa Rican case-control pairs and tested for association with MI. Functional experiments were carried out to determine whether the associated alleles had differences in mRNA expression.Results: The frequency of variant genotype groups did not differ significantly between cases and controls. However, a significant gene x diet interaction was observed, in which, relative to the common 5 repeat allele, the 3 and 4 alleles were associated with a higher MI risk in the high (>= 0.25 g/d) dietary AA group (odds ratio: 1.31; 95% CI: 1.07, 1.61) and with a lower risk in the low (