SLCO1B1 521T?C functional genetic polymorphism and lipid-lowering efficacy of multiple-dose pravastatin in Chinese coronary heart disease patients
| Autor: | Wei Zhang, Lan Fan, Yijing He, Sheng Deng, An Wang, Lian-Ci Wang, Dao-Di Peng, Hong-Hao Zhou, Vural Ozdemir, Gan Zhou, Qi-Ying Xie, Bi-Lian Chen, Wei Xie, Lin-Yong Xu |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Male medicine.medical_specialty Genotype Organic anion transporter 1 Organic Anion Transporters Coronary Disease Pharmacology chemistry.chemical_compound Asian People Internal medicine polycyclic compounds medicine Humans Pharmacology (medical) Prospective Studies Prospective cohort study Aged Pravastatin Polymorphism Genetic biology Liver-Specific Organic Anion Transporter 1 Cholesterol business.industry Anticholesteremic Agents nutritional and metabolic diseases Middle Aged Lipids Hydroxymethylglutaryl-CoA reductase Organic anion-transporting polypeptide Treatment Outcome Endocrinology chemistry Pharmacogenetics biology.protein Female lipids (amino acids peptides and proteins) SLCO1B1 business medicine.drug |
| Zdroj: | British Journal of Clinical Pharmacology. 64:346-352 |
| ISSN: | 1365-2125 0306-5251 |
| Popis: | What is already known about this subject • Both oral clearance as well as delivery of pravastatin to its molecular targets in hepatoctyes are greatly influenced by the organic anion transporting polypeptide 1B1 (OATP1B1), encoded by SLCO1B1. • The role of genetic factors that determine the marked interindividual variability in lipid-lowering efficacy of pravastatin in Chinese patients is not known. • The present study was designed to evaluate the impact of a common functional genetic polymorphism in SLCO1B1 (521TC: Val174Ala) on pravastatin efficacy in Chinese patients with coronary heart disease. What this study adds 521TC functional genetic polymorphism of SLCO1B1 is significantly associated with an attenuated total cholesterol-lowering efficacy of pravastatin in Chinese patients with coronary heart disease. Aims Pravastatin is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, which is widely used both in primary and secondary prevention of coronary heart disease (CHD). Pravastatin is not subject to metabolism by cytochrome P450s, but it is actively transported from blood into target tissues (e.g. hepatocytes in the liver) by the organic anion transporting polypeptide 1B1 (OATP1B1), encoded by SLCO1B1. The aim of the present study was to evaluate the impact of SLCO1B1 521TC (Val174Ala) functional genetic polymorphism on the lipid-lowering efficacy of multiple-dose pravastatin in Chinese patients with CHD. Methods Forty-five hospitalized patients with CHD prospectively received pravastatin as a single-agent therapy (20 mg day−1 p.o.) for 30 days. Serum triglycerides, total cholesterol, low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol concentrations were determined before and after pravastatin treatment. Results Pravastatin treatment significantly decreased plasma lipids in all patients (P 0.05). Conclusions The 521TC polymorphism of SLCO1B1 appears to modulate significantly the total cholesterol-lowering efficacy of pravastatin in Chinese patients with CHD. Further studies are warranted to determine the extent to which SLCO1B1 genetic variation may contribute to resistance to pravastatin in Asian patients treated with standard doses of pravastatin. |
| Databáze: | OpenAIRE |
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