Arachidonate 5-Lipoxygenase Promoter Genotype, Dietary Arachidonic Acid, and Atherosclerosis

Inflammation is believed to have a key role in atherosclerosis. Leukotrienes are important inflammatory mediators generated from arachidonic acid by the enzyme 5-lipoxygenase. This study found that variant genotypes of the 5-lipoxygenase gene, which lacked the common allele, were associated with an increase in intima– media thickness of the carotid artery. A diet high in arachidonic acid further increased the effect of the gene on this measurement. Eicosanoids are lipid mediators of inflammation and hypersensitivity reactions, 1 and arachidonate 5-lipoxygenase is the key enzyme in the oxidative biosynthesis of a class of paracrine and autocrine eicosanoids known as leukotrienes. 2 The dihydroxy leukotriene B 4 is a potent leukocyte chemoattractant, whereas the cysteinyl leukotrienes increase vascular permeability and promote contraction of vascular smooth muscle. 3 The cysteinyl leukotrienes have been linked to asthma, 4 and 5-lipoxygenase promoter genotypes have been identified that interacted strongly with the effects of 5-lipoxygenase inhibition in patients with asthma. 5 , 6 This drug–gene interaction suggested a functional difference in the 5-lipoxygenase pathway between carriers of at least . . .