CYP3AP1*3 allele is associated with lipid-lowering efficacy of simvastatin and atorvastatin in Chinese women.
Response to statin therapy for cardiovascular disease is variable among different individuals. The authors aimed to investigate the effect of the CYP3AP1*3 polymorphism on the lipid-lowering efficacy of statins. They recruited 379 unrelated hyperlipidemic patients: 202 (103 men) treated with simvastatin and 177 (87 men) with atorvastatin as single-agent therapy (20 mg day(-1) orally) for 4 weeks. CYP3AP1*3(-44G>A) was genotyped using the PCR restriction fragment-length polymorphism method. Serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TGs) were determined before and after treatment. The frequency of the CYP3AP1*3 variant allele in Chinese hyperlipidemic patients was 70.6%. In the simvastatin treatment group, the percentage reduction of LDL-C level was greater in the CYP3AP1*3/*3 carriers than in the CYP3AP1*1 carriers. This difference was statistically significant for women but not for men. In contrast, the authors found no significant association between the lipid-lowering efficacy of atorvastatin and the CYP3AP1*3 polymorphism in all participants. However, in women, the percentage change of the TC level was significantly lower in the CYP3AP1*3/*3 carriers than in the CYP3AP1*1 carriers. These findings suggest that the CYP3AP1*3 allele may be a biomarker for the lipid-lowering efficacy of simvastatin and atorvastatin in Chinese women with hyperlipidemia.
Department of Pharmacology, School of Medicine, Zhengzhou University, Zhengzhou 450052, China.
Yan-Peng
YP
Li
Li-Rong
LR
Zhang
Min
M
Jia
Xiang-Jie
XJ
Hu
D000483:Alleles; D044466:Asian People / Q000235:genetics; D000069059:Atorvastatin; D002681:China; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006949:Hyperlipidemias / Q000188:drug therapy; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011446:Prospective Studies; D011758:Pyrroles / Q000494:pharmacology*; D012737:Sex Factors; D019821:Simvastatin / Q000494:pharmacology*
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D011758:Pyrroles; D000069059:Atorvastatin; D019821:Simvastatin; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human