title: The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke.
abstract: 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.
authors.affiliation: deCODE genetics, Sturlugata 8, Reykjavik, Iceland.
authors.forename: Anna
authors.initials: A
authors.lastname: Helgadottir
authors.forename: Andrei
authors.initials: A
authors.lastname: Manolescu
authors.forename: Gudmar
authors.initials: G
authors.lastname: Thorleifsson
authors.forename: Solveig
authors.initials: S
authors.lastname: Gretarsdottir
authors.forename: Helga
authors.initials: H
authors.lastname: Jonsdottir
authors.forename: Unnur
authors.initials: U
authors.lastname: Thorsteinsdottir
authors.forename: Nilesh J
authors.initials: NJ
authors.lastname: Samani
authors.forename: Gudmundur
authors.initials: G
authors.lastname: Gudmundsson
authors.forename: Struan F A
authors.initials: SF
authors.lastname: Grant
authors.forename: Gudmundur
authors.initials: G
authors.lastname: Thorgeirsson
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: Halldor
authors.initials: H
authors.lastname: Johannsson
authors.forename: Olof
authors.initials: O
authors.lastname: Gudmundsdottir
authors.forename: Mark E
authors.initials: ME
authors.lastname: Gurney
authors.forename: Jesus
authors.initials: J
authors.lastname: Sainz
authors.forename: Margret
authors.initials: M
authors.lastname: Thorhallsdottir
authors.forename: Margret
authors.initials: M
authors.lastname: Andresdottir
authors.forename: Michael L
authors.initials: ML
authors.lastname: Frigge
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Topol
authors.forename: Augustine
authors.initials: A
authors.lastname: Kong
authors.forename: Vilmundur
authors.initials: V
authors.lastname: Gudnason
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Gulcher
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
mesh_terms: D058927:5-Lipoxygenase-Activating Proteins; D002352:Carrier Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D002882:Chromosomes, Human, Pair 13; D020022:Genetic Predisposition to Disease; D006801:Humans; D007975:Leukotriene B4 / Q000097:blood; D008565:Membrane Proteins / Q000235:genetics*; D018895:Microsatellite Repeats; D009203:Myocardial Infarction / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D020521:Stroke / Q000235:genetics*
chemical_list: D058927:5-Lipoxygenase-Activating Proteins; C548592:ALOX5AP protein, human; D002352:Carrier Proteins; D008565:Membrane Proteins; D007975:Leukotriene B4