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SLCO1B1 521T-->C functional genetic polymorphism and lipid-lowering efficacy of multiple-dose pravastatin in Chinese coronary heart disease patients.

Abstract：

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 521T-->C (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 < 0.001). Importantly, we showed an attenuated pravastatin pharmacodynamic effect on total cholesterol in patients with 521TC heterozygote genotype (from 5.52 +/- 0.51 mmol l(-1) to 4.70 +/- 0.35 mmol l(-1), % change -14.5 +/- 6.6%, N = 9) compared with 521TT homozygote genotype (from 5.47 +/- 1.15 mmol l(-1) to 4.21 +/- 0.89 mmol l(-1), % change -22.4 +/- 10.3%, N = 36) (mean +/- SD, P = 0.03, two-tailed test with alpha set at 5%). SLCO1B1 521T-->C functional polymorphism did not significantly influence pravastatin pharmacodynamics on other plasma lipids (P > 0.05). CONCLUSIONS:The 521T-->C 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.

journal_name

Br J Clin Pharmacol

journal_title

British journal of clinical pharmacology

authors

Zhang W,Chen BL,Ozdemir V,He YJ,Zhou G,Peng DD,Deng S,Xie QY,Xie W,Xu LY,Wang LC,Fan L,Wang A,Zhou HH

doi

10.1111/j.1365-2125.2007.02892.x

subject

Has Abstract

pub_date

2007-09-01 00:00:00

pages

346-52

issue

eissn

0306-5251

issn

1365-2125

pii

BCP2892

journal_volume

pub_type

临床试验,杂志文章

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SLCO1B1 521T-->C functional genetic polymorphism and lipid-lowering efficacy of multiple-dose pravastatin in Chinese coronary heart disease patients.