Pharmacogenomics and Personalized Medicine (Jun 2022)
Effect of Apolipoprotein E ϵ4 Allele on the Progression of Carotid Atherosclerosis Through Apolipoprotein Levels
Abstract
Wenbing Ma,1,2,* Liting Zhang,1,* Lei Luo,1 Suya Zhang,1,* Shuang Yang,1 Hongping Yao,1 Lei Zhang,1 Xiaoyun Lu,2 Weiyi Feng1 1Department of Pharmacology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China; 2Department 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*These authors contributed equally to this workCorrespondence: Weiyi Feng, Department of Pharmacology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China, Tel/Fax +86-029-85323242, Email [email protected] Xiaoyun Lu, 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, Tel/Fax +86-029-82668463, Email [email protected]: 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.Patients and methods: The study group enrolled 399 CAS participants and 399 non-CAS controls. ApoE gene polymorphisms were determined by Polymerase chain reaction and hybridization.Results: 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.Conclusion: 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.Keywords: apolipoprotein E, carotid atherosclerosis, gene polymorphism, blood lipids
