Apolipoprotein E polymorphisms contribute to statin response in Chinese ASCVD patients with dyslipidemia

Abstract

Background Apolipoprotein E (ApoE) plays an important role in lipid metabolism and clearance. Statins are the most common drugs used to modulate the lipid profile in the clinic therapy; the associations between ApoE polymorphisms and statin response to lipids were inconsistent in previous studies among different ethnicities. Our study aimed to demonstrate the relationships among the statins response and the ApoE gene common polymorphisms and lifestyle risk factors in Chinese arteriosclerotic cardiovascular disease (ASCVD) patients with dyslipidemia. Methods A total of 1002 dyslipidemia ASCVD patients were recruited in this study, including 311 patients with a history of type 2 diabetes mellitus (T2DM). These patients were all treated with drugs atorvastatin (10 mg/d) or rosuvastatin (5 mg/d) for at least 4 weeks and genotyped for ApoE e2/e3/e4 alleles, using Kompetitive Allele Specific PCR (KASP) and Sanger sequencing. The plasma lipids levels were determined before and after statins treatment. Results The results of ApoE genotyping with KASP method were consistent with the sequencing analysis. In the total 1002 patients, the E2 phenotypes (e2/e3, e2/e2) had significant lower low-density lipoprotein cholesterol (LDL-C) baseline levels than subjects with E3 (e3/e3, e2/e4) and E4 (e3/e4, e4/e4) phenotypes ( P = 0.007, 0.005, respectively), and E2 phenotypes had the highest triglyceride (TG) baseline levels. To statins treatment, E2 phenotypes had a better response in TG, Total cholesterol (TC) and LDL-C reduction percentage compared with other phenotypes, and smoking/alcohol drinking status also had a significant influence on statins response of LDL-C lowering. No significant difference was found in the effects of lipids decreasing between atorvastatin and rosuvastatin drugs in all patients. Conclusions We developed the KASP technique for the ApoE genotyping, and demonstrated ApoE polymorphisms interacted with smoking/drinking to influence the declining extent of TG, TC and LDL-C levels after statins therapy in Chinese dyslipidemia ASCVD patients. These discoveries developed our cognition with the genetic polymorphisms effects on statin response, which should be taken more seriously in smoking/drinking E4 amino acid isoform carriers.

Longitudinal and nonlinear relations of dietary and Serum cholesterol in midlife with cognitive decline: results from EMCOA study

“…DNA samples were then randomly placed on batches of 96-well plate. Genotyping of APOE was performed according to the manufacturer’s instructions [21]. For the purpose of quality control, 5% of samples were repeated and non-template controls were set in each plate.…”

Association of APOE polymorphisms with lipid-lowering efficacy of statins in atherosclerotic cardiovascular diseases

“…12,13 Although there have been several studies on the role of APOE polymorphism in lipid-lowering therapy using statins, other studies have reached inconsistent conclusions. 14 The relationship between APOE genotypes and statin efficacy remains controversial and inconclusive. In this study, we investigated a possible correlation between APOE polymorphism and the lipid-lowering efficacy of atorvastatin.…”

“…22 Importantly, a comparison of the lipid-lowering effect among genotypes revealed that ε4 carriers exhibited the smallest decrease in the levels of LDL-C and TC, consistent with findings of previous studies where the ε4 allele seemed to have an inadequate response to statin therapy compared to carriers of other alleles. 23 Age, gender and diseases such as diabetes have been reported as factors that influenced the effectiveness of statins. 24 In our study, baseline characteristics such as age, gender and diseases were similarly distributed among APOE genotypes, which may reduce the factors influencing the lipid-lowering efficacy of statins to an extent.…”

Systematic Pharmacology and GEO Database Mining Revealed the Therapeutic Mechanism of Xuefu Zhuyu Decoration for Atherosclerosis Cardiovascular Disease

“…At present, clinical medications ideas for ASCVD mainly focus on correcting of atherogenic dyslipidemia and platelet aggregation. The clinical efficacy of statins and aspirin has been well-established (5,6). Although current atherosclerosis medications can partially relieve the symptoms of ASCVD patients, gastrointestinal reactions, liver and kidney damage, etc.…”