No impact of SLCO1B1 521T>C, 388A>G and 411G>A polymorphisms on response to statin therapy in the Greek population

被引:26
|
作者
Giannakopoulou, E. [1 ]
Ragia, G. [1 ]
Kolovou, V. [2 ]
Tavridou, A. [1 ,3 ]
Tselepis, A. D. [4 ]
Elisaf, M. [5 ]
Kolovou, G. [2 ]
Manolopoulos, V. G. [1 ,3 ]
机构
[1] Democritus Univ Thrace, Sch Med, Pharmacol Lab, Alexandroupolis 68100, Greece
[2] Onassis Cardiac Surg Ctr, Dept Cardiol, Athens, Greece
[3] Acad Gen Hosp Alexandroupolis, Clin Pharmacol Unit, Alexandroupolis, Greece
[4] Univ Ioannina, Dept Chem, Ioannina, Greece
[5] Univ Ioannina, Sch Med, Dept Internal Med, GR-45110 Ioannina, Greece
关键词
Atorvastatin; Simvastatin; Pharmacogenomics; SLCO1B1; Hypercholesterolemia; Response; DENSITY-LIPOPROTEIN CHOLESTEROL; LIPID-LOWERING EFFICACY; OATP-C SLC21A6; SINGLE NUCLEOTIDE POLYMORPHISMS; TRANSPORTING POLYPEPTIDE 1B1; INDUCED MYOPATHY; HEART-DISEASE; PRAVASTATIN; VARIANTS; GENE;
D O I
10.1007/s11033-014-3334-z
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Interindividual variability exists in statin lipid-lowering response, partially attributed to genetic factors. Organic anion-transporting polypeptide 1B1 (OATP1B1) encoded by SLCO1B1 gene (solute carrier organic anion transporter family member 1B1) facilitates hepatic uptake of simvastatin and atorvastatin. SLCO1B1 polymorphisms are strongly associated with statin-induced myopathy whereas few studies have assessed their effect on statin differential response. In the present study, we analyzed the association of SLCO1B1 521T > C, 388A > G and 411G > A polymorphisms with response to atorvastatin and simvastatin in 386 adults (201 atorvastatin-treated and 185 simvastatin-treated) with primary hypercholesterolemia, all of Greek origin. Total cholesterol and low-density lipoprotein cholesterol were measured at baseline and on 6 months of treatment. Genetic polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. A novel RFLP protocol was developed for the simultaneous identification of 388A > G and 411G > A polymorphisms. SLCO1B1 521T > C, 388A > G and 411G > A polymorphisms were not associated with lipid-lowering response to atorvastatin or simvastatin. No sex-gene or statin dose-gene interaction was observed on the effect of the analyzed SLCO1B1 polymorphisms in statin lipid lowering response in either statin-treated patient cohort. Further studies in different populations are required to draw firm conclusion on the potential association of SLCO1B1 polymorphisms with statin lipid-lowering response.
引用
收藏
页码:4631 / 4638
页数:8
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