Genetic Variants of Arachidonate 5-Lipoxygenase–Activating Protein, and Risk of Incident Myocardial Infarction and Ischemic Stroke: A Nested Case-Control Approach

Background and Purpose— Recent findings have implicated specific gene polymorphisms of arachidonate 5-lipoxygenase–activating protein (ALOX5AP), and 2 at-risk haplotypes (HapA, HapB) in myocardial infarction and stroke. To date, no prospective data are available. Methods— We evaluated 10 specific Icelandic ALOX5AP gene variants among 600 male participants with incident atherothrombotic events (myocardial infarction [MI] or ischemic stroke) and among 600 age- and smoking-matched male participants, all white, who remained free of reported cardiovascular disease during follow-up within the Physicians' Health Study cohort. Results— Overall allele, genotype, and haplotype distributions were similar between cases and controls. Single-marker conditional logistic regression analysis adjusted for potential risk factors found no association with risk of atherothrombotic events. Further investigation using a haplotype-based approach showed similar null findings with MI (HapA: odds ratio [OR]=1.18, 95% CI, 0.76 to 1.85; P=0.46; HapB: odds ratio=0.62, 95% CI, 0.36 to 1.07; P=0.08), and with ischemic stroke (HapA: odds ratio=1.11, 95% CI, 0.65 to 1.89; P=0.71; HapB: odds ratio=0.82, 95% CI, 0.47 to 1.42; P=0.47). Conclusions— We found no evidence for an association of the specific Icelandic ALOX5P gene variants/at-risk haplotypes tested with risk of incident MI nor ischemic stroke in this prospective, non-Icelandic study.