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.