UMR INSERM U1122; Université de Lorraine, Inserm, IGE-PCV, Nancy, France.
EA3998 INRA USC 0340 UR AFPA, Université de Lorraine, 2 ave de la Forêt de Haye, Vandœuvre-lès-Nancy, France.
Neurobiol Aging. 2018 Sep;69:292.e1-292.e5. doi: 10.1016/j.neurobiolaging.2018.04.013. Epub 2018 May 3.
The ε4 allele of the apolipoprotein E (APOE) gene common polymorphism is the strongest genetic risk factor for Alzheimer's disease (AD). Human APOE gene is located on chromosome 19q13.1, a region linked to AD that also includes the LSR gene, which encodes the lipolysis-stimulated lipoprotein receptor (LSR). As an APOE receptor, LSR is involved in the regulation of lipid homeostasis in both periphery and brain. This study aimed to determine the potential interactions between 2 LSR genetic variants, rs34259399 and rs916147, and the APOE common polymorphism in 142 AD subjects (mean age: 73.16 ± 8.50 years) and 63 controls (mean age: 70.41 ± 8.49 years). A significant epistatic interaction was observed between APOE and both LSR variants, rs34259399 (beta = -0.95; p = 2 × 10) and rs916147 (beta = -0.83; p = 6.8 × 10). Interestingly, the interaction of LSR polymorphisms with APOE non-ε4 alleles increased AD risk. This indicates the existence of complex molecular interactions between these 2 neighboring genes involved in the pathogenesis of AD, which merits further investigation.
载脂蛋白 E (APOE) 基因的 ε4 等位基因是阿尔茨海默病 (AD) 的最强遗传风险因素。人类 APOE 基因位于 19q13.1 染色体上，该区域与 AD 相关，其中还包括编码脂解刺激脂蛋白受体 (LSR) 的 LSR 基因。作为 APOE 的受体，LSR 参与外周和大脑中脂质稳态的调节。本研究旨在确定 142 例 AD 患者（平均年龄：73.16 ± 8.50 岁）和 63 名对照者（平均年龄：70.41 ± 8.49 岁）中 2 个 LSR 遗传变异 rs34259399 和 rs916147 与 APOE 常见多态性之间的潜在相互作用。观察到 APOE 与 LSR 变异 rs34259399（beta = -0.95;p = 2 × 10）和 rs916147（beta = -0.83;p = 6.8 × 10）之间存在显著的上位性相互作用。有趣的是，LSR 多态性与 APOE 非 ε4 等位基因的相互作用增加了 AD 的风险。这表明这两个邻近基因在 AD 发病机制中存在复杂的分子相互作用，值得进一步研究。
