Apolipoprotein E Polymorphisms Contribute To Statin Response In Lipid-lowing Therapy

Background Statins could decline the risk of cardiovascular disease(CVD)by reducing the level of cholesterol in plasma,and the effect was different because of the race,drug dosage and even genetic factors.The results of association study between statin response and APOE polymorphisms in lipid-lowing therapy were conflicted,and there was a lack of large group study in Chinese.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 dyslipidemiaMethods 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(10mg/d)or rosuvastatin(5mg/d)for at least 4 weeks,two measurements were obtained for each sample:prior to treatment and 4 weeks post treatment,including TC,TG,LDL-C,HDL-C and non-HDL-C tests.The effect of lipid-lowing therapy was evaluated by the reduction percentages of lipids levels,reduction percentages were calculated as:(baseline lipids leve-after statin therapy lipids level)/(baseline lipids level)*100%APOE genotyped by Sanger sequencing in all 1002 patients,at the same time,we built a new method based on the KASP technology for APOE genotyping.SPSS 22.0 and MDR 3.0.6 were used for statistical analysis of APOE polymorphisms and statin response in lipid-lowing therapy.Machine learning(based on R)was used for prospective analysis.Results The frequencies of E2 isoform(e2/e2,e2/e3)was 164,E3 isoform(e3/e3,e2/e4)was 647,E4 isoform(e 3/e4,e4/e4)was 191.Compare to the E3 and E4 groups,the E2 group has the lowest LDL-C baseline level(P=0.003),and highest TG baseline level(P=0.031).After the statin therapy,the E2 group has the lowest non-HDL-C level compared to the other two groups(P<0.001).For the reduction percentage of lipids,the E2 group has the highest level than E3 and E4 groups in TG,TC,LDL-C,and non-HDL-C(P=0.021,0.012,0.042,0.011).Both in baseline level and after statin therapy,patients with smoking or/and drinking habits have a higher TC level(P=0.005,<0.001),and a lower HDL-C level(P<0.001,<0.001),as also as the increment of HDL-C percentage(P=0.02).For T2DM patients,no matter the baseline level or the lipid level after statin therapy,they have a higher TG level(P<0.001,0.01)and lower HDL-C level(P=0.017,0.007).In all 1002 samples,there is a statistical difference(P=0.0176)among 3 APOE groups when we set the standard-reaching rate as≥25%(LDL-C reduction percentages).In the 433 patients who had statin therapy at least 12 weeks,the statistical differences(P=0.0495,0.0121,respectively)among 3 APOE groups were also existed,when we set the standard-reaching rate as LDL-C<1.8 mmol/L or non-HDL-C<2.6 mmol/L after statin treatment.Smoking,drinking,T2DM and heterozygous of rs7412(T/C)are all harmful factors in lipid-lowing therapy of statins,and smoking or/and drinking habits even destroy the advantages of stain response in E2 group,and for different therapeutic targets,there are different effects of APOE genotypes in statin response.Conclusions We have built a KASP APOE genotyping method,and the APOE E2 isoform group had an advantage in lipid-lowing therapy by statins,the smoking or/and drinking habits could impair the advantage,better living habits management in ApoE4 phenotype patients could be more necessary in the clinical treatment.