CYP3A4*1G polymorphism is associated with lipid-lowering efficacy of atorvastatin but not of simvastatin.
OBJECTIVE
Our aim was to observe the impact of CYP3A4*1G genetic polymorphism on lipid-lowering efficacy of statins.


METHODS
We studied 217 unrelated hyperlipidemic patients who prospectively received atorvastatin and 199 patients who received simvastatin as a single-agent therapy (20 mg day(-1) p.o.) for 4 weeks. Genotyping of CYP3A4*1G was conducted by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were determined before and after treatment by enzymatic assays.


RESULTS
The frequency of CYP3A4*1G in Chinese hyperlipidemic patients was 0.276. After atorvastatin treatment, the mean percentage reduction in serum TC was 16.8 +/- 3.3% (*1/*1), 17.8 +/- 3.8% (*1/*1G), and 20.9 +/- 5.0% (*1G/*1G), respectively. The CYP3A4*1G polymorphism had a gene-dose-dependent effect on percentage reduction in serum TC (P < 0.01). Conversely, there was no significant association between lipid-lowering efficacy of simvastatin and CYP3A4*1G polymorphism.


CONCLUSIONS
Carrying CYP3A4*1G increase the lipid-lowering efficacy of atorvastatin and may have no significant effect on simvastatin treatment.
Department of Pharmacology, School of Medicine, Zhengzhou University, Zhengzhou, China.
Yuan
Y
Gao
Li-rong
LR
Zhang
Qiang
Q
Fu
D000483:Alleles; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics; D000069059:Atorvastatin; D008078:Cholesterol, LDL / Q000097:blood; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use*; D019821:Simvastatin / Q000627:therapeutic use*
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin; D019821:Simvastatin; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human