Tai E Shyong, Ordovas Jose M
Department of Endocrinology, Singapore General Hospital, Department of Medicine and Center for Molecular Epidemiology, National University of Singapore, Singapore.
Curr Opin Lipidol. 2008 Aug;19(4):349-54. doi: 10.1097/MOL.0b013e328304b681.
We have examined the evidence from recent human studies examining the role of apolipoprotein A-V in triglyceride-rich lipoprotein metabolism and cardiovascular disease risk. Special emphasis was placed on the evidence emerging from the association between genetic variability at the apolipoprotein A5 locus, lipid phenotypes and disease outcomes. Moreover, we address recent reports evaluating apolipoprotein A5 gene-environment interactions in relation to cardiovascular disease and its common risk factors.
Several genetic association studies have continued to strengthen the position of APOA5 as a major gene that is involved in triglyceride metabolism and modulated by dietary factors and pharmacological therapies. Moreover, genetic variants at this locus have been significantly associated with both coronary disease and stroke risks.
Apolipoprotein A-V has an important role in lipid metabolism, specifically for triglyceride-rich lipoproteins. However, its mechanism of action is still poorly understood. Clinical significance at present comes largely from genetic studies showing a consistent association with plasma triglyceride concentrations. Moreover, the effects of common genetic variants on triglyceride concentrations and disease risk are further modulated by other factors such as diet, pharmacological interventions and BMI. Therefore, these genetic variants could be potentially used to predict cardiovascular disease risk and individualize therapeutic options to decrease cardiovascular disease risk.
我们研究了近期人体研究的证据,这些研究探讨了载脂蛋白A-V在富含甘油三酯的脂蛋白代谢及心血管疾病风险中的作用。特别强调了载脂蛋白A5基因座的基因变异性、脂质表型和疾病结局之间关联所产生的证据。此外,我们还讨论了近期评估载脂蛋白A5基因-环境相互作用与心血管疾病及其常见危险因素关系的报告。
多项基因关联研究继续巩固了APOA5作为参与甘油三酯代谢且受饮食因素和药物治疗调节的主要基因的地位。此外,该基因座的基因变异与冠心病和中风风险均显著相关。
载脂蛋白A-V在脂质代谢中具有重要作用,特别是对富含甘油三酯的脂蛋白而言。然而,其作用机制仍知之甚少。目前的临床意义很大程度上来自基因研究,这些研究表明其与血浆甘油三酯浓度存在一致的关联。此外,常见基因变异对甘油三酯浓度和疾病风险的影响会受到其他因素(如饮食、药物干预和体重指数)的进一步调节。因此,这些基因变异可能潜在地用于预测心血管疾病风险并使治疗方案个体化,以降低心血管疾病风险。