研究人员检测了血脂代谢过程中的载脂蛋白A5 （APOA5）及编码该蛋白的基因，结果显示携带特异性变异APOA5的个体患心脏病的风险增加，但仅见于同时进食大量omega-6脂肪酸的个体。该项研究发表在《Circulation》杂志上。
Omega-6脂肪酸和omega-3脂肪酸都是多不饱和脂肪酸（PUFAs）。根据美国国立卫生研究所饮食补充剂办公室的一份报告，大多数美国人omega-6脂肪酸的进食量是omega-3脂肪酸的10倍。Omega-3脂肪酸存在于坚果、绿叶蔬菜、肥鱼肉、植物油如芸苔和亚麻子中。而omega-6脂肪酸存在于谷物、肉类、植物油如玉米和黄豆中以及一些加工品中。Omega-6脂肪酸和omega-3脂肪酸都是人体必需脂肪酸，人体自身不能合成而必须靠进食补给。
“我们知道一部分人有心脏病的遗传易患因素，例如血液中LDL-C水平升高。而APOA5在脂蛋白代谢中发挥重要作用，我们想确定某些饮食因素能否改变APOA5在代谢脂蛋白及其成员如甘油三酯（TG）中的作用。” Lai说。
Lai及其同事们发现研究中大约13％的受试者为变异基因携带者。这些携带者中每天进食omega-6脂肪酸含量超过摄入总热卡6％者，其伴有高TG血症，易患动脉粥样硬化（动脉硬化）和心脏病。
美国农业部人类营养研究中心营养与基因组学实验室主任、该项研究的资深作者Jose Ordovas博士说：“以前的研究认为多不饱和脂肪酸如omega-3和omega-6脂肪酸为有益的脂肪酸，认为如果用其代替主要源于动物脂肪的饱和脂肪酸可以通过降低胆固醇水平来降低心脏病风险。”
但是还没有研究表明是否存在一个omega-3脂肪酸与omega-6脂肪酸的最佳比例，或者进食一定量的omega-6脂肪酸可以抵消omega-3的益处。对于携带有变异基因的人来说，进食omega-6脂肪酸就显得重要，因为这可以减少发展成为心脏病的风险。
变异基因携带者中如果每天进食omega-6脂肪酸含量超过每日摄入总热卡的6％，那么个体TG的水平会增高21％，同时血中某些促动脉粥样硬化脂蛋白颗粒水平增高34％。携带者如每天进食omega-6脂肪酸含量低于每日摄入总热卡的6％，则个体没有显示出心脏病危险脂质水平有显著性增高。与omega-6脂肪酸相反，无论是否为APOA5变异基因携带者，omega-3脂肪酸都会降低血中TG及促动脉粥样硬化脂蛋白颗粒的水平。
尽管研究人员分析了多种饮食脂肪，包括饱和脂肪和单不饱和脂肪的资料，饮食与APOA5的相互作用仅见于多不饱和脂肪酸。“这是多不饱和脂肪酸作为脂代谢遗传效应的主要调控者的附加依据。”作者写道。他们继续解释说：“更完整地理解这些因素和更好地利用这些信息有助于筛查易感人群，这些人将会更多地在个性化的饮食建议中受益。”
Ordovas等人还在Journal of Lipid Research上发表另一篇文章，发现大多数APOA5基因变异与颈动脉内膜中层厚度（代表动脉粥样硬化程度的测量指标）不相关，而伴有肥胖的特异性基因变异携带者与颈动脉内膜中层厚度密切相关。”
伴有肥胖的特异性变异基因携带者表达该变异基因的效应不同于不伴肥胖者，表现出粥样斑块更大。这在肥胖受试者中是确定的，无论血脂和血胆固醇、年龄、性别、吸烟、糖尿病、体重指数及血压等被认为是心脏病危险因子的因素有无。Lai提醒说：“尽管肥胖是已知的心脏病促进因子，但这种关联在APOA5变异基因携带者中会被增强。”
“对于某些人来说，预防性干预其饮食和生活方式可能更重要，这与他们的基因构造有关。” Ordovas说。“研究中不好的基因型并不显得那么坏，除非伴有肥胖。”他总结说，“对于健壮的观察者，需要谨慎考虑并通过其他研究证实。同时，以上结果仅限于高加索人群，对其他种族的人群也许不能推广使用。”
Genes and diet linked to risk factors for heart disease
Boston -- Researchers from the Jean Mayer USDA Human Nutrition Research Center (USDA HNRCA) at Tufts University and colleagues have found another link among genes, heart disease and diet. The study, published in Circulation, examined apolipoprotein A5 (APOA5), a gene that codes for a protein, which in turn plays a role in the metabolism of fats in the blood. The results show that people who carry a particular variant of APOA5 may have elevated risk factors that are associated with heart disease, but only if they also consumed high amounts of omega-6 fatty acids in their diets.
Corresponding author Chao-Qiang Lai, PhD, a USDA-Agricultural Research Service (ARS) scientist at the USDA HNRCA, and colleagues analyzed lipid levels and dietary assessment questionnaires of more than 2,000 participants in the Framingham Heart Study and quantified their intake of different types of fats.
Omega-6 fatty acids, as well as omega-3 fatty acids, are polyunsaturated fatty acids (PUFAs) and, according to a report from the National Institutes of Health Office of Dietary Supplements, most Americans consume about 10 times more omega-6s than omega-3s. Omega-3s are found in nuts, leafy green vegetables, fatty fish, and vegetable oils like canola and flaxseed, while omega-6s are found in grains, meats, vegetable oils like corn and soy, and also processed foods made with these oils. Both omega-3s and omega-6s, known as essential fatty acids, must be consumed in the diet because they are not made by the body.
"We know that some people are genetically predisposed to risk factors for heart disease, such as elevated low-density lipoprotein levels in the blood," says Lai, "and that APOA5 has an important role in lipoprotein metabolism. We wanted to determine if certain dietary factors change the role of APOA5 in metabolizing these lipoproteins and their components, such as triglycerides."
Lai and colleagues found that approximately 13 percent of both men and women in the study were carriers of the gene variant. Those individuals that consumed more than six percent of daily calories from omega-6 fatty acids displayed a blood lipid profile more prone to atherosclerosis (hardening of the arteries) and heart disease, including higher triglyceride levels.
Jose Ordovas, PhD, senior author of the study and director of the Nutrition and Genomics Laboratory at the USDA HNRCA, notes that "previous research points to polyunsaturated fatty acids like omega-3s and omega-6s as 'good' fats, thought to reduce risk of heart disease by lowering cholesterol levels if used in place of saturated fats that are mostly found in animal sources."
Ordovas continues, "Research hasn't shown us yet if there is an optimal ratio for omega- 3s to omega-6s, or if consuming a certain amount of omega-6s might negate the benefits of omega-3s. We do know that omega-6s are necessary for the body and can be a source of healthful fat in the diet, but for the 13 percent who are carriers of the particular APOA5 gene variant, consuming fewer omega-6s in relation to omega-3s may be important, as it might help reduce the risk of developing precursors to heart disease."
The carriers of the variant who ate more than six percent of total calories from omega-6s had a 21 percent increase in triglyceride levels, as well as an approximately 34 percent elevation of certain atherogenic lipoprotein particles in the blood.
Carriers who consumed less than six percent of total calories from omega-6s did not show a significant increase in the lipid levels that are risk factors for heart disease. In contrast to omega-6s, higher consumption of omega-3s decreased triglyceride and atherogenic lipoprotein particle levels in the blood, regardless of a person's APOA5 gene variant.
Although the researchers analyzed information on several types of dietary fat, including saturated fat and monounsaturated fat, the interactions between diet and APOA5 were seen only with PUFAs, "adding evidence to the prominent role of PUFAs as modulators of genetic effects in lipid metabolism," write the authors. They go on to explain that "a more complete understanding of these factors and a thoughtful use of this information should help in the identification of vulnerable populations who will benefit from more personalized dietary recommendations."
A second study published by Ordovas, Lai, and colleagues in the Journal of Lipid Research also studied variants of the APOA5 gene in participants in the Framingham Heart Study to determine if the gene is related to atherosclerosis. The authors, including corresponding author Christopher O'Donnell of the National Heart, Lung, and Blood Institute's Framingham Heart Study, and first author Roberto Elosua, a former Fulbright-Generalitat de Catalu馻 fellow who works with Ordovas, found that while most variants of the APOA5 gene were not associated with carotid intimal medial thickness (IMT), a surrogate measure of atherosclerosis burden, particular gene variants were "significantly associated with carotid IMT in obese participants."
Carriers of the particular gene variants who were obese expressed the effects of the gene variant differently than carriers who were not obese, showing a greater build-up of plaque in the heart. This was true for participants who were obese regardless of fat and cholesterol levels in the blood, age, gender, smoking or diabetes status, weight-for-height and blood pressure, all factors which are thought to influence risk of heart disease. Lai notes that "although obesity is a known contributing factor to heart disease, the association was strengthened in carriers of the rare APOA5 variant who were obese."
"It may be more important for some people to make preventive dietary and lifestyle changes than others, depending on their genetic makeup," says Ordovas. "The 'bad' genotype, in this study, doesn't seem to be that bad unless it's triggered by obesity," he concludes. "The observations, while strong, should be considered with caution and confirmed in other studies. Also, the findings were restricted to a Caucasian cohort and may not be generalizable to other ethnic cohorts."
编辑：蓝色幻想
