Apolipoprotein E Gene Polymorphism Effects on Lipid Metabolism and Risk of Cerebral Infarction in Northwest Han Chinese Population.

IF 1.8 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pharmacogenomics & Personalized Medicine Pub Date : 2023-01-01 DOI:10.2147/PGPM.S404663
Yaqi Wang, Shuang Yang, Suya Zhang, Xiaoyu Lu, Wenbing Ma
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Abstract

Background: The apolipoprotein E (ApoE) genetic variation may contribute to the development of Cerebral Infarction (CI). Serum lipid levels are known risk factors for CI, but the effect of the ApoE gene polymorphism on lipid metabolism remains unclear. This retrospective cohort study was designed to determine the role of ApoE genotypes in CI risk and the relationships between ApoE gene polymorphism and serum lipid levels among the population of northwest China.

Patients and methods: 517 CI patients and 517 non-CI controls were enrolled in the study. Polymerase chain reaction and hybridization were utilized to determine the ApoE gene polymorphisms.

Results: The ε3/ε4 genotype and ε4 allele frequency were significantly higher in CI patients than in controls. When stratified by age and sex, statistically significant differences in the distribution and frequency of the ε3/ε4 genotype and ε4 allele were found between patients and controls. Compared to ε2 carriers, ε4 carriers had significantly lower ApoE levels and higher low-density lipoprotein cholesterol (LDL-C), ApoB and ApoB/ApoA-I levels in both two groups. Additionally, control participants with ε4 carriers had significantly higher levels of lipoprotein and total cholesterol (TC) levels than ε2 carriers, while CI patients with ε4 carriers had a significantly lower level of ApoA-I. After adjusting for other established risk factors, drinking, hypertension, lipoprotein, triglycerides (TG) and ε4 allele were significant independent risk factors for CI, which was shown to be associated with a nearly two-fold CI risk.

Conclusion: This study demonstrated that ε4 allele is independent risk factors for CI among patients in Northwest China. ApoE polymorphism was associated with CI, which was partly mediated through blood lipids and may also be mediated through non-lipid pathways. These data might be of great clinical significance in individualized preventive and therapeutic strategies.

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载脂蛋白E基因多态性对西北汉族人群脂质代谢及脑梗死风险的影响
背景:载脂蛋白E (ApoE)基因变异可能与脑梗死(CI)的发生发展有关。血脂水平是已知的CI危险因素,但ApoE基因多态性对脂质代谢的影响尚不清楚。本回顾性队列研究旨在确定ApoE基因型在中国西北人群CI风险中的作用,以及ApoE基因多态性与血脂水平之间的关系。患者和方法:517例CI患者和517例非CI对照纳入研究。采用聚合酶链反应和杂交技术检测ApoE基因多态性。结果:CI患者的ε3/ε4基因型和ε4等位基因频率均显著高于对照组。按年龄和性别分层时,患者与对照组之间ε3/ε4基因型和ε4等位基因的分布和频率差异有统计学意义。与ε2携带者相比,ε4携带者的ApoE水平显著降低,低密度脂蛋白胆固醇(LDL-C)、ApoB和ApoB/ApoA-I水平显著升高。此外,ε4携带者的对照组脂蛋白和总胆固醇水平显著高于ε2携带者,而ε4携带者的CI患者ApoA-I水平显著低于ε2携带者。在调整了其他已确定的危险因素后,饮酒、高血压、脂蛋白、甘油三酯(TG)和ε4等位基因是CI的重要独立危险因素,与CI风险相关近两倍。结论:ε4等位基因是西北地区CI患者的独立危险因素。ApoE多态性与CI相关,部分通过血脂介导,也可能通过非脂质途径介导。这些数据对于制定个体化的预防和治疗策略具有重要的临床意义。
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来源期刊
Pharmacogenomics & Personalized Medicine
Pharmacogenomics & Personalized Medicine Biochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
3.30
自引率
5.30%
发文量
110
审稿时长
16 weeks
期刊介绍: Pharmacogenomics and Personalized Medicine is an international, peer-reviewed, open-access journal characterizing the influence of genotype on pharmacology leading to the development of personalized treatment programs and individualized drug selection for improved safety, efficacy and sustainability. In particular, emphasis will be given to: Genomic and proteomic profiling Genetics and drug metabolism Targeted drug identification and discovery Optimizing drug selection & dosage based on patient''s genetic profile Drug related morbidity & mortality intervention Advanced disease screening and targeted therapeutic intervention Genetic based vaccine development Patient satisfaction and preference Health economic evaluations Practical and organizational issues in the development and implementation of personalized medicine programs.
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