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.
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Acknowledgements
We thank the affected individuals and their families whose contribution made this study possible and the nurses at the Icelandic Heart Association, personnel at the deCODE core facilities, T. Jonsdottir, F. Runarsson, E. Palsdottir, J. Kostic, K. Channer, R. Steeds, R. Singh and P. Braund for their contributions. N.J.S. is supported by the British Heart Foundation.
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Helgadottir, A., Manolescu, A., Thorleifsson, G. et al. The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke. Nat Genet 36, 233–239 (2004). https://doi.org/10.1038/ng1311
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DOI: https://doi.org/10.1038/ng1311
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