Research On The Discrepancy Of Lipid-lowering Effect In Primary Hypercholesterolemia Patients Treated By Pitavastatin

Objective: To analyze the lipid-lowering effect of pitavastatin in primary hyperlipoidemia patients; and to observe the impact of SLCO1B1 521T>C genetic polymorphism and acquired factors on the lipid-lowering effects of pitavastatin in primary hypercholesterolemia patients.Motheds: One hundred and fifty primary hyperlipoidemia patients were screened in our study, acquired characteristics such as sex, age, body mass index and complications were collected before administration. Those patients were randomly divided into two groups by 1:1 ,and treated with pitavastatin 2mg/d or lovastatin 20mg/d respectively at night for 8 weeks.A one-step tetra-primers method(ARMS-PCR)was developed for determination of 521T>C mutation, and Polymerase chain reaction-restriction fragment lengthpolymorphism(PCR-RFLP)was used to identify 388G>A polymorphism in the patients. To analyze the influence of gene and acquired characteristics in the patients treated with pitavastatin. Serum total cholesterol (TC, considered as the main therapeutic index), triglyeride (TG), high-density lipoproteins(HDL)and low-density lipoprotein (LDL) levels were determined before and after . Meanwhile, vital sign, blood and urine routine method,hepatic and renal functions ,adverse reactions those were involved in safety were evaluaed.Results: 1 Comparison of lipid-lowering effect between pitavastatin and lovastatin in primary hypercholesteremia Patients. The difference of baseline characteristics between the two groups showed no statistical significance(P>0.05).The total effective rate of pitavastatin was 83.3%, and the changing of TC,TG,HDL-C and LDL-C were -21.0±5.0%,-25.3±6.8 %,2.4±1.9%and -21.1±6.7% respectively. Meanwhile, The total effective rate of lovastatin was 81.7%, and the changing of TC,TG,HDL-C and LDL-C were -20.4±4.7%,-24.8±6.2 %,2.0±1 .5 % and -20.6±7.8 % respectively. The difference of lipid changing and total effective rate between the two groups showed no statistical significance(P>0.05)2 Genetic polymorphism. The frequencies of the 521T>C and 388G>A variant alleles in primary hypercholesterolemia patients were 71.1% and 11.1%, respectively. Of the patients, 19.3% were heterozygotes , 1.4% were homozygotes, and 79.3% were wild homozygotes for 521T>C variant allele ; and 40.7% were heterozygotes , 50.7%were homozygotes and 8.6% were wild homozygotes for the 388G>A variant allele. The distribution of allele and genotype was consistent with Hardy-Weiberg equilibrium.3 Association of lipid-lowering effect by pitavastatin and 521T>C genotype in primary hypercholesteremia patients: Patients with homozygous for the 521T allele showed an accentuated TC-lowering effect compared with those with 521C allele (-24.3±4.2%vs -11.1±3.4%, P<0.05).We found the differences in the reductions of TG,LDL-C and HDL-C between subjects carrying the wild and mute genotype no statistical significance (P >0.05).4 Results for multifactoring analysis of pi tavastatin: Patients with normal BMI showed an accentuated TC-lowering effect compared with the obesity group(-24.8±4.7 % vs -12.7±3.1 % , P < 0.05). Patients without diabetes mellitus showed an accentuated TC-lowering effect compared with the diabetes mellitus group(-22.2±3.7%vs -12.6±2.9%, P<0.05). By the logistic regression equation: Y = 2.704 - 0.246×X₁-0.222×X₄ - 0.541×X₅ ,χ²=12.112, P<0.05;Conclusions: 1 The lipid-lowering effect was significant and the total effective rate was 83.3% in primary hypercholesterolemia patients after treated with pitavastatin(2mg/d) for 8 weeks.2 The SLCO1B1 521T>C and 388G>A variants are relatively common in primary hypercholesterolemia patients.3 These data suggest that the 521T>C variant of SLCO1B1 attenuates the TC-lowering efficacy of pitavastatin in primary hypercholesterolemia patients; maybe there was influence of obesity and diabetes to the lipid-lowering efficacy.