Abstract
BackgroundApolipoprotein 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.MethodsA 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.ResultsThe 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.ConclusionsWe 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.
Highlights
Apolipoprotein E (ApoE) plays an important role in lipid metabolism and clearance
Lipid profile related to sex, diabetes and lifestyle Females have significantly higher levels in Total cholesterol (TC) and High-density lipoprotein cholesterol (HDL-C) either in the baseline levels (P = 0.005, < 0.001, respectively; Fig. 2a) or after statin treatment (P < 0.001, both; Fig. 2b) than males
The TG and HDL-C baseline levels of dyslipidemia patients with type 2 diabetes mellitus (T2DM) were greater than the patients without diabetes (P < 0.001, = 0.017, respectively)
Summary
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. The combination of three alleles formed six ApoE genotypes: 3 heterozygous (e2/e3, e2/e4 and e3/e4), and 3 homozygous (e2/e2, e3/e3, e4/e4) [6] These ApoE gene polymorphisms of individuals affect the lipoproteins clearing and the lipid profile, which is an important candidate susceptible gene for type Diabetes (T2DM) and/or arteriosclerotic cardiovascular disease (ASCVD) [7,8,9,10]. The E4 phenotype has shown the association with the lower response to the statin therapy in some studies [15,16,17], while there was research reported ApoE polymorphisms showed no significant effect on the response of statin in Chinese patients with hyperlipidemia [18]
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