Center for Cardiovascular Research, Prague, Czech Republic.
Physiol Res. 2009;58 Suppl 2:S101-S110. doi: 10.33549/physiolres.931911.
High plasma levels of triglycerides (TG) are an independent risk factor in the development of cardiovascular disease, with about 50 % of the final levels being determined genetically. Apolipoprotein A5 (APOA5) is the last discovered member of the apolipoprotein APOA1/C3/A4 gene cluster, found by comparative sequencing analysis. The importance of APOA5 gene for determination of plasma triglyceride levels has been suggested after development of transgenic and knock-out mice (transgenic mice displayed significantly reduced TG, whereas knock-out mice had high TG). In Czech population, alleles C-1131 and Trp19 are associated with elevated levels of plasma TG and higher risk of myocardial infarction development. These alleles also play some role in nutrigenetics and actigenetics of lifestyle interventions leading to the plasma cholesterol changes as well as in the pharmacogenetics of statin treatment. On the contrary, APOA5 mutations detected in Czech population did not show strict effect on plasma TG levels. Val153 --> Met variant exhibit the sex-specific effect of HDL-cholesterol levels. The suggested roles of APOA5 variants in determination of the plasma remnant particles, plasma concentrations of C-reactive protein or some anthropometrical parameters were excluded.
血浆甘油三酯（TG）水平升高是心血管疾病发展的独立危险因素，其中约 50%的最终水平受遗传决定。载脂蛋白 A5（APOA5）是通过比较测序分析发现的载脂蛋白 APOA1/C3/A4 基因簇中最后一个被发现的成员。在开发转基因和敲除小鼠后，APOA5 基因对血浆甘油三酯水平的决定作用被提出（转基因小鼠的 TG 水平显著降低，而敲除小鼠的 TG 水平较高）。在捷克人群中，等位基因 C-1131 和 Trp19 与血浆 TG 水平升高和心肌梗死发展风险增加相关。这些等位基因在导致血浆胆固醇变化的营养遗传学和生活方式干预的适应遗传学以及他汀类药物治疗的药物遗传学中也发挥一定作用。相反，在捷克人群中检测到的 APOA5 突变并未对血浆 TG 水平产生严格影响。Val153-->Met 变体表现出高密度脂蛋白胆固醇水平的性别特异性效应。APOA5 变体在决定血浆残粒、C 反应蛋白的血浆浓度或某些人体测量参数方面的作用被排除。
