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TY - JOUR AU - Helgadottir, Anna AU - Manolescu, Andrei AU - Helgason, Agnar AU - Thorleifsson, Gudmar AU - Thorsteinsdottir, Unnur AU - Gudbjartsson, Daniel F AU - Gretarsdottir, Solveig AU - Magnusson, Kristinn P AU - Gudmundsson, Gudmundur AU - Hicks, Andrew AU - Jonsson, Thorlakur AU - Grant, Struan F A AU - Sainz, Jesus AU - O'Brien, Stephen J AU - Sveinbjornsdottir, Sigurlaug AU - Valdimarsson, Einar M AU - Matthiasson, Stefan E AU - Levey, Allan I AU - Abramson, Jerome L AU - Reilly, Murdach P AU - Vaccarino, Viola AU - Wolfe, Megan L AU - Gudnason, Vilmundur AU - Quyyumi, Arshed A AU - Topol, Eric J AU - Rader, Daniel J AU - Thorgeirsson, Gudmundur AU - Gulcher, Jeffrey R AU - Hakonarson, Hakon AU - Kong, Augustine AU - Stefansson, Kari PY - 2006 DA - 2006/01/01 TI - A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction JO - Nature Genetics SP - 68 EP - 74 VL - 38 IS - 1 AB - Variants of the gene ALOX5AP (also known as FLAP) encoding arachidonate 5-lipoxygenase activating protein are known to be associated with risk of myocardial infarction1. 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. SN - 1546-1718 UR - https://doi.org/10.1038/ng1692 DO - 10.1038/ng1692 ID - Helgadottir2006 ER -