载脂蛋白 E 多态性影响脑出血前纵向脂质趋势。
APOE polymorphisms influence longitudinal lipid trends preceding intracerebral hemorrhage.
机构信息
Division of Neurocritical Care and Emergency Neurology (C.-L.P., J.R., C.D.A.), Center for Human Genetic Research (C.-L.P., M.R.R., A.B., J.R., C.D.A.), The J. Philip Kistler Stroke Research Center (A.M.A., M.E.G., A.V., S.M.G., J.R., C.D.A.), Hemorrhagic Stroke Research Group (A.M.A., M.E.G., A.V., S.M.G., J.R., C.D.A.), Division of Behavioral Neurology (A.B.), Division of Psychiatry (A.B.), Department of Psychiatry, Massachusetts General Hospital, Boston; and Program in Medical and Population Genetics (C.-L.P., A.B., J.R., C.D.A.), Broad Institute, Cambridge, MA.
出版信息
Neurol Genet. 2016 Jun 23;2(4):e81. doi: 10.1212/NXG.0000000000000081. eCollection 2016 Aug.
OBJECTIVE
We sought to determine whether APOE genotype influences a previously observed decline in serum total cholesterol (TC) and low-density lipoprotein (LDL) levels preceding primary intracerebral hemorrhage (ICH), as a potential demonstration of nonamyloid mechanisms of APOE in ICH risk.
METHODS
We performed a single-center retrospective longitudinal analysis using patients with known APOE genotype drawn from an ongoing cohort study of ICH. Serum lipid measurements for TC, triglycerides (TGs), LDL, and high-density lipoprotein (HDL) collected within 2 years before and after index ICH were extracted from electronic medical records. Piecewise linear mixed-effects models were used to compare APOE allele-specific effects on temporal serum lipid trends in ICH. Demographics, medical history, medications, and health maintenance data were included as fixed effects. Inter- and intraindividual variations in lipid levels were modeled as random effects.
RESULTS
A total of 124 ICH cases were analyzed. APOE ε4 carriers had greater rates of decline in serum TC and LDL within 6 months preceding ICH (TC: -7.30 mg/dL/mo, p = 0.0035; LDL: -8.44 mg/dL/mo, p = 0.0001). Conversely, serum TC and LDL levels in APOE ε2 carriers were unchanged within the same time period. APOE genotype had no associations with serum HDL or TG trends.
CONCLUSIONS
APOE allele status predicts serum TC and LDL changes preceding acute ICH. Our results have implications for ongoing efforts in dissecting the role of dyslipidemia in cerebrovascular disease risk. APOE genotype-specific influence on lipid trends provides a clue for one mechanism by which APOE may influence risk of ICH. Further characterization of the metabolic roles of APOE is needed to improve the understanding of APOE biology in cerebrovascular disease risk.
目的
我们旨在确定 APOE 基因型是否会影响先前观察到的原发性脑出血（ICH）前血清总胆固醇（TC）和低密度脂蛋白（LDL）水平的下降，这可能是 APOE 在 ICH 风险中发挥非淀粉样机制的一个潜在表现。
方法
我们使用来自正在进行的 ICH 队列研究中已知 APOE 基因型的患者进行了一项单中心回顾性纵向分析。从电子病历中提取了 ICH 前 2 年内和后 2 年内采集的 TC、甘油三酯（TGs）、LDL 和高密度脂蛋白（HDL）的血清脂质测量值。使用分段线性混合效应模型比较 APOE 等位基因对 ICH 中血清脂质趋势的特异性影响。将人口统计学、病史、药物和健康维护数据作为固定效应纳入。将脂质水平的个体内和个体间差异建模为随机效应。
结果
共分析了 124 例 ICH 病例。APOE ε4 携带者在 ICH 前 6 个月内 TC 和 LDL 下降速度更快（TC：-7.30mg/dL/月，p=0.0035；LDL：-8.44mg/dL/月，p=0.0001）。相反，在同一时间段内，APOE ε2 携带者的血清 TC 和 LDL 水平没有变化。APOE 基因型与血清 HDL 或 TG 趋势没有关联。
结论
APOE 等位基因状态预测急性 ICH 前的血清 TC 和 LDL 变化。我们的研究结果对正在进行的剖析血脂异常在脑血管疾病风险中的作用的努力具有重要意义。APOE 基因型对脂质趋势的特定影响提供了一个线索，说明 APOE 可能通过何种机制影响 ICH 的风险。需要进一步表征 APOE 的代谢作用，以提高对 APOE 在脑血管疾病风险中的生物学理解。
Zotero 插件