Correlation Between Polymorphisms Of ApoE Gene And The Lipid Regulatory Effect Of Atorvastatin

Objective:To study the relationship of ApoE restricted fragment length polymorphism and the therapeutic effect by atorvastatin, and the influence to hepatic function.The study provided an important foundation for the gene-directed rationalization and individualization of medication in the hyperlipidemic patients.Methods:Subjects and Genotyping A group of 49 Han Chinese hyperlipidemic patients[total cholesterol (TC)>6mmol·L-1 or triglycerides (TG)>1.78 mmol·L-1 or low-denstity lipoprotein cholesterol (LDL-C)>3.36 mmol·L-1 or high-denstity lipoprotein cholesterol (HDL-C)<0.82mmol·L-1] were recruited from hospitalized patients in a hospital. Venous blood(～1mL) was obtained from the patients and DNA was isolated from peripheral leucocytes. Genotyping of ApoE alleles were conducted by the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. Genotype and allelic frequencies were calculated by gene counting.Evaluation of efficacy of atorvastatin The hyperlipidemic patients were treated with 20mg atorvastatin daily for 4 weeks. The blood samples were obtained for lipids and hepatic function testing or DNA extraction before and after 4 weeks of treatment. The levels of serum TC, TG, LDL-C, HDL-C, Apoa and ALP, AST, STB, BA, ALT were measured by using Enzymatic in fasting condition. The effects measured at week 4 were the mean percentage change in TC, TG, LDL-C, HDL-C and Apoa from baseline; The hepatic dysfunction measured at week 4 were the mean percentage change in ALP, AST, STB, BA and ALT from baseline. We observed the effect of ApoE2, ApoE3 and ApoE4 genetic polymorphism on the lipid-lowering and hepatic function-changing efficacy by atorvastatin.Statistical analysis The hyperlipidemic patients were divided into three groups according to the alleles, and allele frequencies were estimated from the observed numbers of each specific allele. SPSS 13.0 software was used for statistical analyses. Chi-square test was used to verify Hardy-Weinberg equilibrium. t test was used to compare the levels among before and after treatment. ANOVA was used to compare the differences in the lipid-lowering and change of hepatic function effects of atorvastatin. P-value<0.05 was considered statistically significant.Results:The ApoE genetype and allelic frequency was consistent with Hardy-Weinberg equilibrium.Baseline of lipid did not show significant difference in three groups; after oral intake of atorvastatin 20mg daily for 4 weeks, all the levels of TC, TG, LDL-C decreased than before treatment. The changed percentage of TC was the largest in the four levels; and the percentage of TG changed was the smallest.After 4 weeks treatment, the group carrying E2 allele had more responsive(P<0.05) to atorvastatin than E3 and E4 alleles in total cholesterol(TC). Compared the changed value of lipids according to different alleles, we found that there were no significant differences about the change of TC, TG, LDL-C, HDL-C and Apoa. The ApoE locus did not account for any significant fraction of the variability in response.At the same time, the levels of STB, BA and ALT increased after 4 weeks treatment in every groups. STB (18±0.51%) and ALT (31±0.93%) changed worse in the group carrying E3 allele, but we found that there were no significant differences between all groups.Conclusion:1.Patients carrying E2 allele was more prominent efficacy than non-carrying E2 allele; ApoE genetic polymorphism did not influence lipid-lowering efficacy of atorvastatin.2. ApoE genetic polymorphism had no significant effect on adverse reactions of hepatic function.3. Satisfactory lipid-lowering efficacy was obtained by hyperlipidemic patients with taking atorvastatin 20mg daily after 4 weeks.