| Literature DB >> 14770184 |
Anna Helgadottir1, Andrei Manolescu, Gudmar Thorleifsson, Solveig Gretarsdottir, Helga Jonsdottir, Unnur Thorsteinsdottir, Nilesh J Samani, Gudmundur Gudmundsson, Struan F A Grant, Gudmundur Thorgeirsson, Sigurlaug Sveinbjornsdottir, Einar M Valdimarsson, Stefan E Matthiasson, Halldor Johannsson, Olof Gudmundsdottir, Mark E Gurney, Jesus Sainz, Margret Thorhallsdottir, Margret Andresdottir, Michael L Frigge, Eric J Topol, Augustine Kong, Vilmundur Gudnason, Hakon Hakonarson, Jeffrey R Gulcher, Kari Stefansson.
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.Entities:
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Year: 2004 PMID： 14770184 DOI： 10.1038/ng1311
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330