Study Finds Genetic Link to Atherosclerosis
]]>Atherosclerosis]]> is the buildup of plaque in the arteries, which causes them to become hard and narrow. This hardening and narrowing of the arteries plays a major role in the development of ]]>heart attacks]]> and ]]>strokes]]> .
]]>Elevated cholesterol]]> and ]]>triglyceride]]> levels, ]]>high blood pressure]]> , tobacco smoke, ]]>diabetes]]> , and a variety of other factors can potentially damage the lining of arterial walls, an early step in the development of atherosclerosis. Damage to arterial walls sets up an inflammatory response, which helps initiate plaque formation. As plaque is deposited in the arteries, they become hard and narrow, which increases the chances that a blood clot will form, leading to a heart attack or stroke.
Researchers have known for many years that atherosclerosis has a genetic link (it tends to run in families), but the genetic markers that contribute to atherosclerosis are only beginning to be discovered. A new study in the January 1, 2004 issue of the New England Journal of Medicine found that a certain gene variation was associated with thickened arteries. Furthermore, certain fatty acids in the diet significantly affected artery thickness in people with the variation, but not others.
About the Study
This study included 470 men and women ages 40–60 who had not been diagnosed with ]]>cardiovascular disease]]> . The researchers took ultrasounds to measure the thickness of the walls of the carotid artery (a major artery in the neck), which is considered a marker for atherosclerosis. They also analyzed the participants’ DNA to determine which variation of the 5-lipoxygenase (ALOX5) gene (thought to be involved in the development of atherosclerosis) the participants carried—the common form or the variant form. Since certain fatty acids are thought to promote atherosclerosis, while others are thought to help prevent it, the participants provided six 24-hour records of their food intake for 1.5 years so that the researchers could assess fatty acid consumption.
The researchers used these data to determine whether the ALOX5 gene affected artery thickness. They also compared the effects of fatty acid intake in people with the common form of gene to those with the variant form.
The researchers found that 442 of the participants (94%) carried the common form of the gene and 28 (6%) carried the variant form. The participants with the variation had significantly thicker arteries than those with the common form of the gene. In fact, the effect of the ALOX5 gene variation on artery thickness was similar to the effect of having diabetes, and less than the effect of smoking.
In participants with the variation, the intake of certain fatty acids was linked with artery thickness. Among these participants, higher intake of arachidonic acid (found in meats) and linoleic acid (found in some vegetable oils) was associated with increased artery thickness. Higher intake of omega-3 fatty acids (found in fish oils), on the other hand, was associated with decreased artery thickness. Fatty acid intake, however, did not affect the artery thickness of the participants with the common form of the gene.
While these results are interesting and important, they are limited by the fact that the researchers used carotid artery thickness as marker for atherosclerosis. A more reliable study would be one that followed carriers and non-carriers of the ALOX 5 gene variations over time to see if who was more likely to develop heart disease, strokes or other complications of atherosclerosis.
How Does This Affect You?
This study is the first of many future studies to reveal a link between a specific gene and the risk of atherosclerosis. While the ALOX5 gene variation is relatively rare—only 6% of the participants in this study carried it—it has the potential to be used as a genetic marker for atherosclerosis. If the individuals who carry the variation could be easily identified, they and their physicians could be more proactive in the diagnosis, prevention, and treatment of atherosclerosis.
A particularly interesting aspect of this study is that diet had a significant impact on the artery thickness in people who carried the variation. In these people, higher intake of foods rich in arachidonic and linoleic fatty acids (like meat and certain vegetable oils) were associated with thicker artery walls, while higher intakes of omega-3 fatty acids (rich in oily fish) were associated with decreased artery thickness. This is consistent with a number of studies that have shown a decreased risk of coronary artery disease and stroke in certain people who consume a diet rich in fish.
Since a test to check the status of your ALOX5 gene will probably not be available for some time, how can you benefit from these findings? This study further supports an important nutrition message: the type of fat you eat may be as—or more—important than the amount of fat you eat. To help protect the health of your arteries, replace saturated or trans fats with polyunsaturated and monounsaturated fats (i.e., vegetable oils, nuts, seeds, and avocados), but still keep a limit on the amount of oils you consume. And increase your intake of fish, particularly those rich in the omega-3 fatty acids like mackerel, herring, sardines, albacore tuna, and salmon. The American Heart Association recommends eating at least two servings of fish per week.
American Heart Association
National Heart, Lung, and Blood Institute
Atherosclerosis. American Heart Association website. Available at: http://www.americanheart.org/ . Accessed December 31, 2003.
Atherosclerosis: what is atherosclerosis? National Heart, Lung, and Blood Institute website. Available at: http://dci.nhlbi.nih.gov/ . Accessed December 31, 2003.
Dwyer JH, Allaye H, Dwyer KM, et al. Arachidonate 5-lipoxygenase promoter genotype, dietary arachidonic acid, and atherosclerosis. New England Journal of Medicine . 2004;350:29-37.
Fish and omega-3 fatty acids. American Heart Association website. Available at: http://www.americanheart.org/ . Accessed January 2, 2004.
Last reviewed Jan 2, 2004 by ]]>Richard Glickman-Simon, MD]]>
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