Biology Faculty Articles


A Variant of the Gene Encoding Leukotriene A4 Hydrolase Confers Ethnicity-Specific Risk of Myocardial Infarction


Anna Helgadottir, deCODE Genetics, Inc.
Andrei Manolescu, deCODE Genetics, Inc.
Agnar Helgason, deCODE Genetics, Inc.
Gudmar Thorleifsson, deCODE Genetics, Inc.
Unnur Thorsteinsdottir, deCODE Genetics, Inc.
Daniel F. Gudbjartsson, deCODE Genetics, Inc.
Solveig Gretarsdottir, deCODE Genetics, Inc.
Kristinn P. Magnusson, deCODE Genetics, Inc.
Gudmundur Gudmundsson, deCODE Genetics, Inc.
Andrew Hicks, deCODE Genetics, Inc.
Thorlakur Jonsson, deCODE Genetics, Inc.
Struan F. A. Grant, deCODE Genetics, Inc.
Jesus Sainz, deCODE Genetics, Inc.
Stephen J. O'Brien, National Cancer Institute at FrederickFollow
Sigurlaug Sveinbjornsdottir, National University Hospital - Reykjavik, Iceland
Einar M. Valdimarsson, National University Hospital - Reykjavik, Iceland
Stefan E. Matthiasson, National University Hospital - Reykjavik, Iceland
Allan I. Levey, Emory University School of Medicine
Jerome L. Abramson, Emory University School of Medicine
Murdach P. Reilly, University of Pennsylvania
Viola Vaccarino, Emory University School of Medicine
Megan L. Wolfe, University of Pennsylvania
Vilmundur Gudnason, Icelandic Heart Association
Arshed A. Quyyumi, Emory University School of Medicine
Eric J. Topol, Cleveland Clinic Foundation
Daniel J. Rader, University of Pennsylvania
Gudmundur Thorgeirsson, National University Hospital - Reykjavik, Iceland
Jeffrey R. Gulcher, deCODE Genetics, Inc.
Hakon Hakonarson, deCODE Genetics, Inc.
Augustine Kong, deCODE Genetics, Inc.
Kari Stefansson, deCODE Genetics, Inc.

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Nature Genetics







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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.


©2006 Nature Publishing Group

Additional Comments

NIH grant #s: U54 ES012068, P50 HL077107-01; Emory General Clinic Research Center grant #: MO1-RR00039





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