Lack of association between SLCO1B1 polymorphism and the lipid-lowering effects of atorvastatin and simvastatin in Chinese individuals

• Published in: European journal of clinical pharmacology 2013-06, Vol.69 (6), p.1269-1274
• Main Authors: Fu, Qiang, Li, Yan-Peng, Gao, Yuan, Yang, Song-Hua, Lu, Pei-Qi, Jia, Min, Zhang, Li-Rong
• Format: Article
• Language: English
• Subjects: Adult; Aged; Analysis of Variance; Asian Continental Ancestry Group - genetics; Atorvastatin; Biological and medical sciences; Biomarkers - blood; Biomedical and Life Sciences; Biomedicine; Chi-Square Distribution; China; Cholesterol, HDL - blood; Cholesterol, LDL - blood; Cytochrome P-450 CYP3A - genetics; Cytochrome P-450 CYP3A - metabolism; Female; Gene Frequency; Genetics; Haplotypes; Heptanoic Acids - therapeutic use; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias - blood; Hyperlipidemias - drug therapy; Hyperlipidemias - ethnology; Hyperlipidemias - genetics; Lipids; Liver-Specific Organic Anion Transporter 1; Male; Medical sciences; Middle Aged; Organic Anion Transporters - genetics; Organic Anion Transporters - metabolism; Pharmacogenetics; Pharmacology; Pharmacology. Drug treatments; Pharmacology/Toxicology; Phenotype; Polymerase Chain Reaction; Polymorphism; Polymorphism, Single Nucleotide; Pyrroles - therapeutic use; Simvastatin - therapeutic use; Statins; Treatment Outcome; Triglycerides - blood
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-012-1453-9

Purpose There is significant inter-individual variability in the lipid-lowering effects of atorvastatin and simvastatin. Our goal was to investigate the impact of SLCO1B1 genetic polymorphism on the lipid-lowering effects of atorvastatin and simvastatin. Methods We recruited 363 unrelated hyperlipidemic patients with the CYP3A4 * 1 /* 1 , CYP3A5 * 1 /* 1 , and CYP3AP1 * 1 /* 1 genotypes: 189 of these were treated with atorvastatin and 174 were treated with simvastatin as a single-agent therapy (20 mg day −1 orally) for 4 weeks. The genotyping of SLCO1B1 c.521T > C (p.V174A, OATP - C * 5 ) was performed with allele-specific polymerase chain reaction (AS-PCR), and PCR restriction fragment length polymorphism (RFLP) was performed to detect the carriers of SLCO1B1 c.388A > G (p.N130D, OATP-C*1b). Serum triglyceride (TGs), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were determined before and after treatment. Results The frequencies of the SLCO1B1 521T > C and 388A > G variant alleles in Chinese hyperlipidemic patients were found to be 16.2% and 72.1% respectively. After treatment with 20 mg simvastatin or atorvastatin daily for 4 weeks, TC, TG, and LDL-C concentrations were lower than at baseline, on average, by 18.1 ± 3.7%, 25.8 ± 9.7%, 27.7 ± 5.4% in the simvastatin-treated group, and 17.5 ± 3.7%, 22.6 ± 8.6%, 27.5 ± 5.5% in the atorvastatin-treated group respectively, and the mean relative reduction in serum HDL cholesterol did not reach statistical significance (−1.0 ± 10.9%, 0.5 ± 9.3%). However, no significant differences were observed in the lipid-lowering effects of atorvastatin and simvastatin between subjects with different SLCO1B1 genotypes. Conclusion The SLCO1B1 521T > C and 388A > G variants were found to be relatively common in Chinese patients with essential hyperlipidemia. These frequencies were found to be similar to those observed in healthy Chinese and Japanese individuals, but significantly different from Caucasians and blacks. SLCO1B1 521T > C and 388A > G polymorphisms may not be associated with the lipid-lowering effects of atorvastatin and simvastatin.