The effects of CYP3A4*18A, CYP3A4*18B and MDR1 C3435T polymorphisms on plasma concentration and efficacy of atorvastatin / 中国药学杂志
Chinese Pharmaceutical Journal
;
(24): 1682-1689, 2016.
Artigo
em Chinês
| WPRIM
| ID: wpr-858958
ABSTRACT
OBJECTIVE:
To investigate the interindividual variabilities of plasma concentration and lipid-regulating efficacy of atorvastatin in patients with hyperlipidemia through the genotyping of CYP3A4*18A, *18B and MDR1 C3435T genes.METHODS:
One hundred and fifteen Chinese Han population with hyperlipidemia were genotyped by the PCR-RFLP (restriction fragment length polymorphism). The steady-state plasma trough concentrations of atorvastatin were measured by high performance liquid chromatography (HPLC)-UV. The levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were monitored by the homogeneous enzyme method before treatment and 1 month after medication.RESULTS:
The mutation frequencies of CYP3A4*18A, *18B and MDR1 C3435T were 3.48%, 23.48% and 31.74% respectively. It shows no statistically significant difference for the SNPs frequencies between the normal population reported and patients selected. Patients with CYP3A4*18B homozygous mutant (AA) showed a significantly higher plasma concentration of ATV compared with the G/A heterozygous mutat patients or the G/G wild-type homozygous (P=0.016). However, no significant difference could be shown in the patients with CYP3A4*18A and MDR1 C3435T genotypes(P>0.05). Neither CYP3A4*18A nor MDR1 C3435T could be shown a significant difference in the lipid lowering efficiency(P>0.05). Patients carrying the homozygous mutant (AA) of the CYP3A4*18B gene showed a significantly higher TC lipid-regulating effect compared with patients with the GA or GG genetic variant (P=0.02). The LDL-C change rates among the three genotype groups were significantly different, with AA group >GA group >GG group (P=0.01) and the regulation of TG and HDL-C for AA, GA or GG was compared without finding any significant difference (P>0.05). The TC changerates and plasma concentration were significantly correlated (P=0.031) before and after treatment, while there was no statistical significance in the correlation of the other three lipid change rates with plasma concentration (P>0.05).CONCLUSION:
The SNPs MDR1 C3435T and CYP3A4*18A do not affect the plasma concentration and efficacy of ATV. In ATV therapy, patients with the CYP3A4*18B gene exhibit higher plasma concentrations than the non-carriers, and the lipid-lowering efficacy was more pronounced.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Idioma:
Chinês
Revista:
Chinese Pharmaceutical Journal
Ano de publicação:
2016
Tipo de documento:
Artigo
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