van de Woestijne Anton P, van der Graaf Yolanda, de Bakker Paul I W, Asselbergs Folkert W, Spiering Wilko, Visseren Frank L J
Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
PLoS One. 2014 Jun 30;9(6):e101082. doi: 10.1371/journal.pone.0101082. eCollection 2014.
Single nucleotide polymorphisms in the APOA5-A4-C3-A1 gene complex are associated with elevated plasma triglycerides and elevated vascular risk in healthy populations. In patients with clinically manifest vascular disease, hypertriglyceridemia and metabolic syndrome are frequently present, but the contribution of these single nucleotide polymorphisms to plasma triglycerides, effect modification by obesity and risk of recurrent vascular events is unknown in these patients.
Prospective cohort study of 5547 patients with vascular disease. Rs964184 (APOA5-A4-C3-A1 gene complex) was genotyped, and we evaluated the relation with plasma lipid levels, presence of metabolic syndrome and the risk for new vascular events.
The minor allele of rs964184 was strongly associated with log plasma triglycerides (β 0.12; 95%CI 0.10-0.15, p = 1.1*10(-19)), and was also associated with 0.03 mmol/L lower high-density lipoprotein-cholesterol (95%CI 0.01-0.04), and 0.14 mmol/L higher non-high-density lipoprotein-cholesterol (95%CI 0.09-0.20). The minor allele frequency increased from 10.9% in patients with plasma triglycerides <1 mmol/L to 24.6% in patients with plasma triglycerides between 4 and 10 mmol/L. The relation between rs964184 and plasma triglycerides was modified by body mass index in patients with one minor allele (β 0.02; (95%CI -0.04-0.09) if body mass index <24 kg/m2, β 0.17 (95%CI 0.12-0.22) if body mass index >27 kg/m2, p for interaction = 0.02). The prevalence of the metabolic syndrome increased from 52% for patients with two copies of the major allele to 62% for patients with two copies of the minor allele (p = 0.01). Rs964184 was not related with recurrent vascular events (HR 0.99; 95%CI 0.86-1.13).
The single nucleotide polymorphism rs964184 (APOA5-A4-C3-A1) is associated with elevated plasma triglycerides concentrations in patients with clinically manifest vascular disease. In carriers of one minor allele, the effect on plasma triglycerides was modified by body mass index. There is no relation between rs964184 and recurrent vascular events in these patients.
载脂蛋白A5-A4-C3-A1基因复合体中的单核苷酸多态性与健康人群血浆甘油三酯升高及血管风险增加相关。在有临床症状的血管疾病患者中，高甘油三酯血症和代谢综合征很常见，但这些单核苷酸多态性对血浆甘油三酯的影响、肥胖的效应修饰作用以及复发性血管事件的风险在这些患者中尚不清楚。
对5547例血管疾病患者进行前瞻性队列研究。对rs964184（载脂蛋白A5-A4-C3-A1基因复合体）进行基因分型，并评估其与血浆脂质水平、代谢综合征的存在以及新血管事件风险的关系。
rs964184的次要等位基因与血浆甘油三酯对数显著相关（β 0.12；95%置信区间0.10 - 0.15，p = 1.1×10⁻¹⁹），还与高密度脂蛋白胆固醇降低0.03 mmol/L（95%置信区间0.01 - 0.04）以及非高密度脂蛋白胆固醇升高0.14 mmol/L（95%置信区间0.09 - 0.20）相关。次要等位基因频率从血浆甘油三酯<1 mmol/L的患者中的10.9%增加到血浆甘油三酯在4至10 mmol/L之间的患者中的24.6%。在携带一个次要等位基因的患者中，rs964184与血浆甘油三酯之间的关系受到体重指数的修饰（如果体重指数<24 kg/m²，β 0.02；（95%置信区间 - 0.04 - 0.09），如果体重指数>27 kg/m²，β 0.17（95%置信区间0.12 - 0.22），交互作用p = 0.02）。代谢综合征的患病率从携带两个主要等位基因拷贝的患者中的52%增加到携带两个次要等位基因拷贝的患者中的62%（p = 0.01）。rs964184与复发性血管事件无关（风险比0.99；95%置信区间0.86 - 1.13）。
单核苷酸多态性rs964184（载脂蛋白A5-A4-C3-A1）与有临床症状的血管疾病患者血浆甘油三酯浓度升高相关。在携带一个次要等位基因的携带者中，对血浆甘油三酯的影响受到体重指数的修饰。在这些患者中，rs964184与复发性血管事件无关。
