Pharmacogenetic analysis of lipid responses to rosuvastatin in Chinese patients

  title={Pharmacogenetic analysis of lipid responses to rosuvastatin in Chinese patients},
  author={Miao Hu and Sandra S.H. Lui and Valiant Wah Lun Mak and Tanya Ten Wah Chu and Vivian Wing Yan Lee and Emily WM Poon and Teresa Kam Chi Tsui and Gary T. C. Ko and Larry Baum and Lai-Shan Tam and Edmund Kwok-Ming Li and Brian Tomlinson},
  journal={Pharmacogenetics and Genomics},
Lipid changes with statin treatments vary greatly between individuals for reasons which are largely unknown. This study was performed to examine the genetic determinants of lipid responses to rosuvastatin in Chinese patients. A total of 125 polymorphisms in 61 candidate genes from 386 Chinese patients were analyzed for association with the lipid responses to rosuvastatin 10 mg daily. The polymorphisms most highly associated with the low-density lipoprotein cholesterol (LDL-C) response were 421C… 
Intronic variants in SLCO1B1 related to statin-induced myopathy are associated with the low-density lipoprotein cholesterol response to statins in Chinese patients with hyperlipidaemia
The intronic SNP rs4149081 in SLCO1B1 was associated with the LDL-C response to statins in Chinese patients and this association was independent of the 521T>C polymorphism.
Effects of Phenotypic and Genotypic Factors on the Lipid Responses to Niacin in Chinese Patients With Dyslipidemia
Baseline lipid levels were the main determinants of lipid responses especially for LDL-C, and the DGAT2 rs3060 polymorphism might influence the lipid responses depending on baseline phenotype, but this association did not persist after adjustment for the baseline lipid levels.
The farnesoid X receptor -1G>T polymorphism influences the lipid response to rosuvastatin[S]
The association of the variant allele of the FXR -1G>T polymorphism with a greater LDL-C response to rosuvastatin may suggest that this polymorphism influences the expression of the hepatic efflux transporters involved in biliary excretion of rosuVastatin.
Personalised medicine in hypercholesterolaemia: the role of pharmacogenetics in statin therapy
Genetic assessment for specific known SNPs within the most known genes appears likely to predict the efficacy of statin therapy and prevent their side effects but does not necessarily reduce the risk of cardiovascular events.
Effects of polymorphisms in ABCG2, SLCO1B1, SLC10A1 and CYP2C9/19 on plasma concentrations of rosuvastatin and lipid response in Chinese patients.
It is suggested that the increased plasma concentrations of rosuvastatin in Chinese patients are associated with increased lipid-lowering effects and lower doses of roSuvastsatin should be effective in subjects with the ABCG2 421C>A variant.
Pharmacogenomics of statins and familial hypercholesterolemia
The variability in low-density lipoprotein cholesterol reductions on statin therapy is still an important factor that needs to be addressed to ensure better cardiovascular disease risk management, especially for FH patients, who have not been well studied historically in this context.
Seventeen years of statin pharmacogenetics: a systematic review.
There is no evidence for the value of genetic testing in clinical practice for statins associations as effect sizes are modest and none of the investigated SNPs consistently affected the risk reduction for cardiovascular events.
Pharmacokinetics and Genetic Factors of Atorvastatin in Healthy Korean Subjects
The pharmacokinetic properties of atorvastatin in Koreans are different from those in Caucasians and that atorVastatin AUC0–24 h could be predicted based on age and eight genetic variants of ABCB1, ABCG2, APOA5, CETP, and CYP7A1.
Impact of Pharmacogenetics on Efficacy and Safety of Statin Therapy for Dyslipidemia
A statin‐based summary of available evidence describing pharmacogenetic associations that may be of clinical relevance in the future is provided, suggesting currently available studies may be useful in providing direction for future confirmatory studies and may point to associations that could be confirmed when more patient outcomes–based studies are available.


Pharmacogenetics of HMG-CoA Reductase Inhibitors: Optimizing the Prevention of Coronary Heart Disease
Pharmacogenetic and pharmacogenomic studies of statin therapy are likely to provide a better understanding of the effects of these drugs and to help with prediction of the most appropriate drug and dosage for each individual and whether the addition or substitution of other lipid modifying drugs may be necessary to achieve the most safe and effective prevention of coronary heart disease.
ABCG2 Polymorphism Is Associated With the Low‐Density Lipoprotein Cholesterol Response to Rosuvastatin
In 305 Chinese patients with hypercholesterolemia who were treated with rosuvastatin at a dosage of 10 mg daily, the c.421A variant was found to be significantly associated with greater reduction in LDL‐C level, in a gene‐dose‐dependent manner.
Hepatic Metabolism and Transporter Gene Variants Enhance Response to Rosuvastatin in Patients With Acute Myocardial Infarction: The GEOSTAT-1 Study
The LDL cholesterol target was achieved more frequently for the 1 in 3 patients with CYP3A5 and/or BCRP variant genotypes when prescribed rosuvastatin 10 mg, compared with simvastsatin 40 mg.
Role of BCRP 421C>A polymorphism on rosuvastatin pharmacokinetics in healthy Chinese males.
ABCG2 Polymorphism Markedly Affects the Pharmacokinetics of Atorvastatin and Rosuvastatin
The results indicate that the ABCG2 polymorphism markedly affects the pharmacokinetics of atorvastatin and, even more so, of rosuvastsatin—potentially affecting the efficacy and toxicity of statin therapy.
A Review of the Pharmacologic and Pharmacokinetic Aspects of Rosuvastatin
  • C. M. White
  • Biology, Medicine
    Journal of clinical pharmacology
  • 2002
Rosuvastatin is an agent with molecular alterations that provide it with unique pharmacologic and pharmacokinetic effects and is a novel and unique HMG‐CoA reductase inhibitor for the treatment of hyperlipidemia.
Polymorphism of the hepatic influx transporter organic anion transporting polypeptide 1B1 is associated with increased cholesterol synthesis rate
It is concluded that the low activity SLCO1B1 c.521CC genotype is associated with an increased cholesterol synthesis rate and the short-term effects of statins on cholesterol homeostasis were not associated with the S LCO1 B1 polymorphism.
Human flavin-containing monooxygenases.
Although exhaustive examples are not available, physiological factors can influence FMO function, and this may have implications for the clinical significance of FMO and a role in human disease.