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

作者: James H. Dwyer , Hooman Allayee , Kathleen M. Dwyer , Jing Fan , Huiyun Wu

DOI: 10.1056/NEJMOA025079

关键词:

摘要: background Leukotrienes are inflammatory mediators generated from arachidonic acid (polyunsaturated ni6 fatty acid) by the enzyme 5-lipoxygenase. Since atherosclerosis involves arterial inflammation, we hypothesized that a polymorphism in 5-lipoxygenase gene promoter could relate to humans and this effect interact with dietary intake of competing substrates. methods We determined genotypes, carotid-artery intima–media thickness, markers inflammation randomly sampled cohort 470 healthy, middle-aged women men Los Angeles Atherosclerosis Study. Dietary marine ni3 acids (including substrate reduces production leukotrienes) were measured use six 24-hour recalls food intake. results Variant genotypes (lacking common allele) found 6.0 percent cohort. Mean ( ± SE) thickness adjusted for age, sex, height, racial or ethnic group was increased 80 19 µm (95 confidence interval, 43 116; P<0.001) among carriers two variant alleles, as compared (wild-type) allele. In multivariate analysis, increase alleles (62 µm, similar associated diabetes (64 P=0.01), strongest cardiovascular risk factor. Increased significantly enhanced apparent atherogenic genotype, whereas blunted effect. Finally, plasma level C-reactive protein, marker factor 2 conclusions identify subpopulation atherosclerosis. The observed diet–gene interactions further suggest polyunsaturated promote, inhibit, leukotriene-mediated leads subpopulation.

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