The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke
The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke
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DOI：
10.1038/ng1311
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发表时间：
2004-03-01
期刊：
影响因子：
30.8
通讯作者：
Stefansson, K
中科院分区：
文献类型：
--
作者：
Helgadottir, A;Manolescu, A;Stefansson, K
我们将一个易感的心肌梗塞的基因映射到13q12-13染色体上的基因座。跨越编码5-脂氧合酶激活蛋白（瓣）基因的基因座中的四个标记单核苷酸多态性（SNP）单倍型与冰岛心肌梗塞的风险更大有关。这种单倍型也赋予了中风风险的两倍。另一个ALOX5AP单倍型与英国个体的心肌梗塞有关。与对照组中的中性粒细胞相比，来自心肌梗死个体的刺激性嗜中性粒细胞产生的白细胞3（在5-脂氧合酶途径中是一种关键产物，这是5-脂氧合酶途径中的关键产物），这种差异主要归因于携带高风险单倍型的男性的细胞。我们得出的结论是，Alox5ap的变体通过增加白细胞产生和动脉壁的炎症来参与心肌梗塞和中风的发病机理。
We mapped a gene predisposing to myocardial infarction to a locus on chromosome 13q12-13. A four-marker single-nucleotide polymorphism (SNP) haplotype in this locus spanning the gene ALOX5AP encoding 5-lipoxygenase activating protein (FLAP) is associated with a two times greater risk of myocardial infarction in Iceland. This haplotype also confers almost two times greater risk of stroke. Another ALOX5AP haplotype is associated with myocardial infarction in individuals from the UK. Stimulated neutrophils from individuals with myocardial infarction produce more leukotriene B4, a key product in the 5-lipoxygenase pathway, than do neutrophils from controls, and this difference is largely attributed to cells from males who carry the at-risk haplotype. We conclude that variants of ALOX5AP are involved in the pathogenesis of both myocardial infarction and stroke by increasing leukotriene production and inflammation in the arterial wall.