Study On The Association Among The Body Mass Index, The Polymorphisms Of CYP3A4*18B And OATP1B1Genes With The Effectivity Of Atorvastatin

Objective： This study is to analyaze metabolic enzymes (CYP3A4*18B),transporter (OATP1B1) gene polymorphism in the different BMI patients, which isexpected to reveal the source of the individual differences of atorvastatin, and toprovide the experiment basis for realizing more precise personalized atorvastatin lipidtreatment.Method:The general information and blood samples of121cases of atorvastatin treatedwith hyperlipidemia were collected in equilibrium patients. According to the BMIindex, patients were divided into obese group, overweight group, and normal group.After4weeks of atorvastatin(20mg qd) treatment the serum lipids and otherbiochemical parameters of patients were tested contrast to baseline (beforemedication). Gene polymorphism of CYP3A4*18B and OATP1B1388G> A wasanalized by polymerase chain reaction restriction fragment length polymorphism(PCR-RFLP) method. The plasma concentration of atorvastatin was determined byHPLC method. The safety and efficacy of atorvastatin was observed.Results：1According to OATP1B1and CYP3A4*18B genotype, all the subjects weredivided into three groups, AA (15), AG (43) and GG (63); CYP3A4wild type was*1/*1(47) and*1/*18B (56) while the variant was*18B/*18B (18). The genotypemutation frequency of OATP1B1388A>G and CYP3A4*18B are70.1%(171)and38.0%(92) in121patients, respectively. 2There are36,47and38cases in obesity group, overweight group and normalgroup, respectively. Atorvastatin reducing the LDL-C of the obese patients and theoverweight patients is obviously superior to the normal patients (P <0.0l). TheHDL-C was significantly increased by atorvastatin in the obese patients (P <0.0l).Compared with the normal weight patients and overweight patients, plasmaconcentration of atorvastatin was significantly higher in the obese patients (P <0.0l).3The TC reduction by atorvastatin was stronger in patients with CYP3A418B/*18B and CYP3A4*1/*18B genotype than that in patients with CYP3A4*1/*1genotype (P<0.0l, P<0.05). Atorvastatin which increase the HDL-C in theCYP3A418B/*18B patients is higher than that in the CYP3A4*1/*18B patients(P<0.05), The plasma concentration of atorvastatin is obviously higher in patientswith CYP3A4*18B/*18B genotype than that in patients with CYP3A4*1/*18Band CYP3A4*1/*1genotye (P<0.0l，P<0.05), but no difference was observed inthe latter two groups of patients.4The TC, TG, HDL-C, LDL-C and ApoB had no significant difference in patients ofOATP1B1388G> A genotypes treated with atorvastatin. However, the steady stateplasma concentration of atorvastatin was significantly higher in homozygousmutant patients than that in mutant heterozygous and homozygous wild typepatients (P <0.0l).Conclusion：1The effectivity of atorvastatin on the obese and overweight patients was betterthan those of normal weight patients.2The effectivity of atorvastatin on the patients with CYP3A4*18B genotype wassignificantly enhanced.3The effectivity of atorvastatin was not affected on the patients by OATP1B1388genotype.4Atorvastatin was safety in patients of each BMI group.