title: A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction.
abstract: 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.
authors.affiliation: deCODE Genetics, Inc., Sturlugata 8, IS-101 Reykjavik, Iceland.
authors.forename: Anna
authors.initials: A
authors.lastname: Helgadottir
authors.forename: Andrei
authors.initials: A
authors.lastname: Manolescu
authors.forename: Agnar
authors.initials: A
authors.lastname: Helgason
authors.forename: Gudmar
authors.initials: G
authors.lastname: Thorleifsson
authors.forename: Unnur
authors.initials: U
authors.lastname: Thorsteinsdottir
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Gudbjartsson
authors.forename: Solveig
authors.initials: S
authors.lastname: Gretarsdottir
authors.forename: Kristinn P
authors.initials: KP
authors.lastname: Magnusson
authors.forename: Gudmundur
authors.initials: G
authors.lastname: Gudmundsson
authors.forename: Andrew
authors.initials: A
authors.lastname: Hicks
authors.forename: Thorlakur
authors.initials: T
authors.lastname: Jonsson
authors.forename: Struan F A
authors.initials: SF
authors.lastname: Grant
authors.forename: Jesus
authors.initials: J
authors.lastname: Sainz
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: O'Brien
authors.forename: Sigurlaug
authors.initials: S
authors.lastname: Sveinbjornsdottir
authors.forename: Einar M
authors.initials: EM
authors.lastname: Valdimarsson
authors.forename: Stefan E
authors.initials: SE
authors.lastname: Matthiasson
authors.forename: Allan I
authors.initials: AI
authors.lastname: Levey
authors.forename: Jerome L
authors.initials: JL
authors.lastname: Abramson
authors.forename: Murdach P
authors.initials: MP
authors.lastname: Reilly
authors.forename: Viola
authors.initials: V
authors.lastname: Vaccarino
authors.forename: Megan L
authors.initials: ML
authors.lastname: Wolfe
authors.forename: Vilmundur
authors.initials: V
authors.lastname: Gudnason
authors.forename: Arshed A
authors.initials: AA
authors.lastname: Quyyumi
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Topol
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Rader
authors.forename: Gudmundur
authors.initials: G
authors.lastname: Thorgeirsson
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Gulcher
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
authors.forename: Augustine
authors.initials: A
authors.lastname: Kong
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
mesh_terms: D001741:Black or African American / Q000235:genetics*; D044383:Black People / Q000235:genetics*; D016022:Case-Control Studies; D004851:Epoxide Hydrolases / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007055:Iceland; D015810:Linkage Disequilibrium; D008969:Molecular Sequence Data; D009203:Myocardial Infarction / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D004851:Epoxide Hydrolases; C043134:leukotriene A4 hydrolase