A gene encoding 5-lipoxygenase activating protein (FLAP), known as ALOX5AP, was found to increase the risk of myocardial infarction and stroke. A four-SNP haplotype in this gene was associated with a two-fold increased risk of myocardial infarction and stroke in Iceland. This haplotype was also linked to myocardial infarction in UK individuals. Neutrophils from individuals with myocardial infarction produced more leukotriene B4, a key product in the 5-lipoxygenase pathway, than those from controls, with this difference largely attributed to males carrying the at-risk haplotype. These findings suggest that variants of ALOX5AP contribute to the pathogenesis of myocardial infarction and stroke by increasing leukotriene production and inflammation in the arterial wall. Cardiovascular diseases are the leading causes of death and disability in the developed world, with a rising prevalence due to aging and obesity. Myocardial infarction and stroke account for over a million deaths annually. The processes underlying myocardial infarction include atherosclerosis with arterial wall inflammation, involving monocyte diapedesis, neutrophil and macrophage activation, and cytokine release. However, the genetic basis of these processes remains unclear. Two approaches have been used to identify genes associated with myocardial infarction: testing SNPs in candidate genes and case-control association studies. While some proinflammatory genes have been associated with increased risk, the genetic basis of myocardial infarction remains undetermined. Genome-wide scans in families with myocardial infarction have identified several loci, but the underlying genes have not been identified. A genome-wide scan of 296 Icelandic families identified ALOX5AP as a gene associated with myocardial infarction and stroke. A four-SNP haplotype in ALOX5AP was associated with a two-fold increased risk of myocardial infarction and stroke. FLAP regulates the 5-lipoxygenase pathway, which is involved in atherosclerosis. Males with the at-risk haplotype had significantly higher production of leukotriene B4, supporting the role of proinflammatory activity in myocardial infarction. The association of ALOX5AP with myocardial infarction was confirmed in a British cohort. The study also found that the at-risk haplotype was associated with stroke and peripheral arterial occlusive disease (PAOD). In a British cohort, the haplotype was more common in males with myocardial infarction than in females. Additionally, the haplotype was associated with ischemic and hemorrhagic stroke in males. The study suggests that ALOX5AP is the first gene isolated that confers substantial population-attributable risk for myocardial infarction and stroke. The findings indicate that ALOX5AP plays a significantA gene encoding 5-lipoxygenase activating protein (FLAP), known as ALOX5AP, was found to increase the risk of myocardial infarction and stroke. A four-SNP haplotype in this gene was associated with a two-fold increased risk of myocardial infarction and stroke in Iceland. This haplotype was also linked to myocardial infarction in UK individuals. Neutrophils from individuals with myocardial infarction produced more leukotriene B4, a key product in the 5-lipoxygenase pathway, than those from controls, with this difference largely attributed to males carrying the at-risk haplotype. These findings suggest that variants of ALOX5AP contribute to the pathogenesis of myocardial infarction and stroke by increasing leukotriene production and inflammation in the arterial wall. Cardiovascular diseases are the leading causes of death and disability in the developed world, with a rising prevalence due to aging and obesity. Myocardial infarction and stroke account for over a million deaths annually. The processes underlying myocardial infarction include atherosclerosis with arterial wall inflammation, involving monocyte diapedesis, neutrophil and macrophage activation, and cytokine release. However, the genetic basis of these processes remains unclear. Two approaches have been used to identify genes associated with myocardial infarction: testing SNPs in candidate genes and case-control association studies. While some proinflammatory genes have been associated with increased risk, the genetic basis of myocardial infarction remains undetermined. Genome-wide scans in families with myocardial infarction have identified several loci, but the underlying genes have not been identified. A genome-wide scan of 296 Icelandic families identified ALOX5AP as a gene associated with myocardial infarction and stroke. A four-SNP haplotype in ALOX5AP was associated with a two-fold increased risk of myocardial infarction and stroke. FLAP regulates the 5-lipoxygenase pathway, which is involved in atherosclerosis. Males with the at-risk haplotype had significantly higher production of leukotriene B4, supporting the role of proinflammatory activity in myocardial infarction. The association of ALOX5AP with myocardial infarction was confirmed in a British cohort. The study also found that the at-risk haplotype was associated with stroke and peripheral arterial occlusive disease (PAOD). In a British cohort, the haplotype was more common in males with myocardial infarction than in females. Additionally, the haplotype was associated with ischemic and hemorrhagic stroke in males. The study suggests that ALOX5AP is the first gene isolated that confers substantial population-attributable risk for myocardial infarction and stroke. The findings indicate that ALOX5AP plays a significant