Helgadottir Anna, Manolescu Andrei, Helgason Agnar, Thorleifsson Gudmar, Thorsteinsdottir Unnur, Gudbjartsson Daniel F, Gretarsdottir Solveig, Magnusson Kristinn P, Gudmundsson Gudmundur, Hicks Andrew, Jonsson Thorlakur, Grant Struan F A, Sainz Jesus, O'Brien Stephen J, Sveinbjornsdottir Sigurlaug, Valdimarsson Einar M, Matthiasson Stefan E, Levey Allan I, Abramson Jerome L, Reilly Murdach P, Vaccarino Viola, Wolfe Megan L, Gudnason Vilmundur, Quyyumi Arshed A, Topol Eric J, Rader Daniel J, Thorgeirsson Gudmundur, Gulcher Jeffrey R, Hakonarson Hakon, Kong Augustine, Stefansson Kari
deCODE Genetics, Inc., Sturlugata 8, IS-101 Reykjavik, Iceland.
Nat Genet. 2006 Jan;38(1):68-74. doi: 10.1038/ng1692. Epub 2005 Nov 10.
Variants of the gene ALOX5AP (also known as FLAP) encoding arachidonate 5-lipoxygenase activating protein are known to be associated with risk of myocardial infarction. Here we show that a haplotype (HapK) spanning the LTA4H gene encoding leukotriene A4 hydrolase, a protein in the same biochemical pathway as ALOX5AP, confers modest risk of myocardial infarction in an Icelandic cohort. Measurements of leukotriene B4 (LTB4) production suggest that this risk is mediated through upregulation of the leukotriene pathway. Three cohorts from the United States also show that HapK confers a modest relative risk (1.16) in European Americans, but it confers a threefold larger risk in African Americans. About 27% of the European American controls carried at least one copy of HapK, as compared with only 6% of African American controls. Our analyses indicate that HapK is very rare in Africa and that its occurrence in African Americans is due to European admixture. Interactions with other genetic or environmental risk factors that are more common in African Americans are likely to account for the greater relative risk conferred by HapK in this group.
已知编码花生四烯酸5-脂氧合酶激活蛋白的ALOX5AP基因（也称为FLAP）的变体与心肌梗死风险相关。在此我们表明，一个跨越编码白三烯A4水解酶的LTA4H基因的单倍型（单倍型K），该蛋白与ALOX5AP处于相同的生化途径，在冰岛人群队列中赋予了适度的心肌梗死风险。白三烯B4（LTB4）生成的测量结果表明，这种风险是通过白三烯途径的上调介导的。来自美国的三个队列也表明，单倍型K在欧洲裔美国人中赋予了适度的相对风险（1.16），但在非裔美国人中赋予的风险则大三倍。约27%的欧洲裔美国对照携带至少一个单倍型K拷贝，相比之下，非裔美国对照中只有6%携带。我们的分析表明，单倍型K在非洲非常罕见，其在非裔美国人中的出现是由于欧洲人基因混合。与其他在非裔美国人中更常见的遗传或环境风险因素的相互作用，可能是单倍型K在该群体中赋予更大相对风险的原因。
