Ma Wenbing, Zhang Liting, Luo Lei, Zhang Suya, Yang Shuang, Yao Hongping, Zhang Lei, Lu Xiaoyun, Feng Weiyi
Department of Pharmacology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, People's Republic of China.
Department of Biological Science and Bioengineering, Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, People's Republic of China.
Pharmgenomics Pers Med. 2022 Jun 21;15:653-661. doi: 10.2147/PGPM.S367471. eCollection 2022.
The apolipoprotein E (ApoE) genetic variation may be involved in the development of Carotid Atherosclerosis (CAS) disease. So far, few data are available on the role of ApoE isoforms in CAS. The association between this ApoE genotype and CAS remains controversial. The aim of this study was to investigate ApoE gene polymorphism in relation to CAS and the relationships between ApoE gene polymorphism and plasma lipid levels in the ShaanXi Han populations.
The study group enrolled 399 CAS participants and 399 non-CAS controls. ApoE gene polymorphisms were determined by Polymerase chain reaction and hybridization.
The ε3/ε4 genotype and ε4 allele in patients with CAS were significantly higher than control participants. In stratified analyses by age and sex, the elevated risk conferred by ɛ4 allele was evident in adults under 60 years old, but not in adults over 60 years old, females and males. ε4 carriers had significantly elevated ApoB and ApoB/ApoA and decreased ApoE levels than ε2 carriers in CAS patients. After adjusting for confounding factors, hypertension, ApoA-I, low density lipoprotein cholesterol (LDL-C), triglycerides (TG) and ε4 allele were significant independent risk factor for CAS. ApoE-ε4 allele was associated with a nearly 1.5-fold increased risk of CAS.
This study provides convincing evidence that ε4 allele, hypertension, ApoA-I, LDL-C and TG levels are independent risk factor for CAS in the ShaanXi Han populations. ApoE polymorphism was associated with CAS and this association was partly mediated through blood lipids. Also, the clinical use of genomic data may become useful in optimizing individual preventative and therapeutic strategies.
载脂蛋白E（ApoE）基因变异可能参与颈动脉粥样硬化（CAS）疾病的发生发展。迄今为止，关于ApoE异构体在CAS中的作用的数据较少。这种ApoE基因型与CAS之间的关联仍存在争议。本研究的目的是调查陕西汉族人群中ApoE基因多态性与CAS的关系以及ApoE基因多态性与血脂水平之间的关系。
研究组纳入399例CAS参与者和399例非CAS对照。通过聚合酶链反应和杂交确定ApoE基因多态性。
CAS患者的ε3/ε4基因型和ε4等位基因显著高于对照参与者。在按年龄和性别进行的分层分析中，ε4等位基因带来的风险升高在60岁以下成年人中明显，但在60岁以上成年人、女性和男性中不明显。在CAS患者中，ε4携带者的ApoB和ApoB/ApoA显著升高，ApoE水平低于ε2携带者。在调整混杂因素后，高血压、载脂蛋白A-I、低密度脂蛋白胆固醇（LDL-C）、甘油三酯（TG）和ε4等位基因是CAS的显著独立危险因素。ApoE-ε4等位基因与CAS风险增加近1.5倍相关。
本研究提供了令人信服的证据，表明ε4等位基因、高血压、载脂蛋白A-I、LDL-C和TG水平是陕西汉族人群中CAS的独立危险因素。ApoE多态性与CAS相关，这种关联部分通过血脂介导。此外，基因组数据的临床应用可能有助于优化个体预防和治疗策略。
