Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA, USA.
Am J Clin Nutr. 2012 Oct;96(4):917-22. doi: 10.3945/ajcn.112.040907. Epub 2012 Aug 22.
The apolipoprotein A5 gene (APOA5) is a major gene that regulates lipid metabolism and is modulated by dietary factors. A novel variant rs964184 in APOA5 was identified to be associated with lipids in genome-wide association studies.
We examined whether this variant modified changes in lipid concentrations in response to a 2-y weight-loss diet intervention in a randomized trial.
The current analyses were secondary analyses of a data set from the Pounds Lost Trial. We genotyped APOA5 rs964184 in 734 overweight or obese adults who were randomly assigned to one of 4 diets that differed in percentages of energy derived from fat, protein, and carbohydrate for 2 y. We evaluated changes in fasting serum concentrations of total cholesterol (TC), LDL cholesterol, HDL cholesterol, and triglyceride from baseline to 2 y of follow-up.
After a 2-y dietary intervention, we showed significant interactions between the APOA5 rs964184 polymorphism and dietary fat intake (low compared with high) in the determination of changes in TC, LDL cholesterol, and HDL cholesterol (P-interaction = 0.007, 0.017, and 0.006, respectively). In the low-fat intake group (20% of energy derived from fat), carriers of the risk allele (G allele) exhibited greater reductions in TC and LDL cholesterol than did noncarriers (P = 0.036 and 0.039, respectively), whereas in the high-fat diet group (40% of energy derived from fat), participants with the G allele had a greater increase in HDL cholesterol than did participants without this allele (P = 0.038).
Our data showed better improvement in lipid profiles from long-term low-fat diet intake in the APOA5 rs964184 risk allele.
载脂蛋白 A5 基因（APOA5）是调节脂质代谢的主要基因，受饮食因素调节。在全基因组关联研究中发现，APOA5 中的一个新变体 rs964184 与脂质有关。
我们在一项随机试验中检查了该变体是否改变了对 2 年减肥饮食干预的脂质浓度变化。
当前分析是 Pounds Lost 试验数据集的二次分析。我们对 734 名超重或肥胖成年人进行了 APOA5 rs964184 基因分型，这些成年人被随机分配到 4 种不同脂肪、蛋白质和碳水化合物能量百分比的饮食组中，进行了 2 年的随访。我们评估了从基线到 2 年随访期间空腹血清总胆固醇（TC）、LDL 胆固醇、HDL 胆固醇和甘油三酯浓度的变化。
经过 2 年的饮食干预，我们发现 APOA5 rs964184 多态性与饮食脂肪摄入（低与高）之间存在显著的相互作用，这决定了 TC、LDL 胆固醇和 HDL 胆固醇的变化（P 交互=0.007、0.017 和 0.006）。在低脂肪摄入组（20%的能量来自脂肪）中，风险等位基因（G 等位基因）携带者的 TC 和 LDL 胆固醇降低幅度大于非携带者（P=0.036 和 0.039），而在高脂肪饮食组（40%的能量来自脂肪）中，携带 G 等位基因的参与者的 HDL 胆固醇升高幅度大于不携带该等位基因的参与者（P=0.038）。
我们的数据显示，APOA5 rs964184 风险等位基因从长期低脂肪饮食摄入中改善了血脂谱。
