NEW YORK (Reuters Health) - Polymorphisms in the promoter region of the 5-lipoxygenase gene seem to increase the risk of atherosclerosis, according to a report published in the January 1st issue of The New England Journal of Medicine. However, diet has a strong modulating effect.
Lipoxygenase converts arachidonic acid into leukotrienes, well-known inflammatory mediators. Therefore, any genetic variants that enhance the enzyme’s ability to catalyze this reaction could possibly result in greater inflammation and, as result, atherosclerosis.
Dr. James W. Dwyer, from the University of Southern California in Los Angeles, and colleagues tested for 5-lipoxygenase gene variants in 470 healthy, middle-aged adults. Carotid-artery intima-media thickness and markers of inflammation were measured in all subjects and they were surveyed to determine dietary intake of arachidonic acid and omega-3 fatty acids.
Six percent of subjects had a variant 5-lipoxygenase genotype, the researchers note. Compared with subjects who had two wild-type alleles, carriers of two variant alleles had significantly increased intima-media thickness. In fact, the increased thickness found in such carriers was comparable to that seen with diabetes, the strongest heart disease risk factor.
As anticipated, consumption of diets high in arachidonic acid seems to enhance the atherogenic effect of the variant alleles. In contrast, diets high in omega-3 fatty acids --which are competing 5-lipoxygenase substrates -- blunted this effect.
Consistent with the pro-inflammatory effects of leukotrienes, the authors found that C-reactive protein levels were increased in carriers of two variant lipoxygenase alleles.
“These findings could lead to new dietary and targeted molecular approaches to the prevention and treatment of cardiovascular disease according to genotype,” the researchers conclude.
Source: N Engl J Med 2004;350:29-37. [ Google search on this article ]
MeSH Headings:Hormone Antagonists: Hormones, Hormone Substitutes, and Hormone Antagonists: Leukotriene B4: Membrane Proteins: Receptors, Cell Surface: Receptors, Eicosanoid: Receptors, Leukotriene: Leukotriene Antagonists: Chemical Actions and Uses: Chemical Actions: Chemicals and DrugsCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
