IGE-PCV, Université de Lorraine, Nancy 54000, France.
Inserm, C3M, Team Control of Gene Expression (10), Université Cote d'Azur, Nice, France.
Aging (Albany NY). 2022 Mar 28;14(6):2524-2536. doi: 10.18632/aging.203984.
The Apolipoprotein E () genotype has been shown to be the strongest genetic risk factor for Alzheimer's disease (AD). Moreover, both the lipolysis-stimulated lipoprotein receptor (LSR) and the vascular endothelial growth factor A (VEGF-A) are involved in the development of AD. The aim of the study was to develop a prediction model for AD including single nucleotide polymorphisms (SNP) of , and VEGF-A-related variants. The population consisted of 323 individuals (143 AD cases and 180 controls). Genotyping was performed for: the common polymorphism (rs429358 and rs7412), two variants (rs34259399 and rs916147) and 10 VEGF-A-related SNPs (rs6921438, rs7043199, rs6993770, rs2375981, rs34528081, rs4782371, rs2639990, rs10761741, rs114694170, rs1740073), previously identified as genetic determinants of VEGF-A levels in GWAS studies. The prediction model included direct and epistatic interaction effects, age and sex and was developed using the elastic net machine learning methodology. An optimal model including the direct effect of the allele, age and eight epistatic interactions between and , and VEGF-A-related variants was developed with an accuracy of 72%. Two epistatic interactions (rs7043199rs6993770 and rs2375981rs34528081) were the strongest protective factors against AD together with the absence of allele. Based on pathway analysis, the involved variants and related genes are implicated in neurological diseases. In conclusion, this study demonstrated links between , and VEGF-A-related variants and the development of AD and proposed a model of nine genetic variants which appears to strongly influence the risk for AD.
载脂蛋白 E () 基因型已被证明是阿尔茨海默病 (AD) 的最强遗传风险因素。此外，脂肪酶刺激的脂蛋白受体 (LSR) 和血管内皮生长因子 A (VEGF-A) 都参与了 AD 的发展。本研究的目的是开发一种包括载脂蛋白 E 基因单核苷酸多态性 () 、血管内皮生长因子 A 相关变体的 AD 预测模型。该人群由 323 人组成（143 例 AD 病例和 180 例对照）。进行了基因分型：常见多态性 (rs429358 和 rs7412)、两个变体 (rs34259399 和 rs916147) 和 10 个血管内皮生长因子 A 相关 SNP(rs6921438、rs7043199、rs6993770、rs2375981、rs34528081、rs4782371、rs2639990、rs10761741、rs114694170、rs1740073)，这些 SNP 先前被确定为 GWAS 研究中血管内皮生长因子 A 水平的遗传决定因素。预测模型包括直接和上位性相互作用效应、年龄和性别，并使用弹性网络机器学习方法进行开发。开发了一个包括等位基因的直接效应、年龄和载脂蛋白 E 与血管内皮生长因子 A 相关变体之间的 8 个上位性相互作用的最佳模型，其准确性为 72%。两个上位性相互作用（rs7043199rs6993770 和 rs2375981rs34528081）是最强的保护性因素，与不存在等位基因一起，共同对抗 AD。基于途径分析，所涉及的变体和相关基因与神经疾病有关。总之，本研究证明了载脂蛋白 E 与血管内皮生长因子 A 相关变体之间的联系与 AD 的发展，并提出了一个包含九个遗传变异的模型，该模型似乎强烈影响 AD 的风险。
