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The effects of a single nucleotide polymorphism in SLCO1B1 on the pharmacodynamics of pravastatin
Author(s) -
Martin Nicholas G.,
Li Ka Wah,
Murray Heather,
Putt Wendy,
Packard Chris J.,
Humphries Steve E.
Publication year - 2012
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2011.04090.x
Subject(s) - pravastatin , pharmacodynamics , slco1b1 , medicine , single nucleotide polymorphism , pharmacology , statin , simvastatin , endocrinology , pharmacokinetics , crossover study , genotype , cholesterol , biology , genetics , alternative medicine , pathology , gene , placebo
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The SNP rs4149056 is associated with altered statin pharmacokinetics and increased risk of statin intolerance. LDL‐cholesterol lowering by simvastatin is also affected by rs4149056 but differences between the genotypes are small. Studies of the effect of rs4149056 on pravastatin pharmacodynamics have been inconclusive. WHAT THIS PAPER ADDS • rs4149056 was not associated with an altered lipid or CRP response to 40 mg day −1 pravastatin in more than 600 high risk men from Scotland, suggesting that the rs4149056 genotype does not significantly affect pravastatin efficacy. AIM To determine whether the SNP rs4149056 in SLCO1B1 alters the pharmacodynamics of pravastatin. METHODS rs4149056 was genotyped in 626 pravastatin‐treated participants in the WOSCOPS trial and the response after 1 year of treatment was compared between the different genotypes. RESULTS Pravastatin reduced serum LDL cholesterol by 22.2% in TT homozygotes, by 22.2% in TC heterozygotes and by 17.7% in CC homozygotes (TT + TC vs . CC P value 0.33). There were no significant differences in the response of total cholesterol, LDL, HDL, triglycerides or CRP to pravastatin between the genotypes. CONCLUSION The rs4149056 SNP did not significantly affect the pharmacodynamics of pravastatin.