Effect of SLCO1B1 Gene Polymorphism on Lipid - Lowering Effect of Atorvastatin

Abstract

Abstract: Objective To study the effect of SLCO1B1 gene polymorphism on the lipid-lowering effect of atorvastatin. Methods Patients who had been taking atorvatatin for more than 15 days with complete clinical records were recruited ,and patients taking other lipid-lowerring medicines or with other lipid-related factors were excluded. The clinical data and serum lipid levels before and after atorvastatin treatment were collected, and SLCO1B1 -521T> C （rs4149056） and -388A> G （rs2306283） gene polymorphisms were detected. Results The results showed that the genotype distribution of patients was consistent with the Hardy-Weinberg equilibrium （P>0.05）. The reduction of TC, LDL-C and TG in SLCO1B1 -388GG genotype subgroup was significantly higher than that in AA+AG genotype subgroup. Conclusion SLCO1B1 polymorphism, especially -388A>G had significantly effect on the lipid-lowering effect of atorvastatin.

Key words: atorvastatin calcium, SLCO1B1, gene polymorphism, serum lipid levels

CLC Number:

ZHANG Ya-tong, ZHU Kong-cai, ZHAO Ming, ZHAO Zi-nan, LI Zheng, HE Yi-jun. Effect of SLCO1B1 Gene Polymorphism on Lipid - Lowering Effect of Atorvastatin[J]. Chinese Journal of Pharmacovigilance, 2017, 14(5): 274-277.

References

[1] Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries （the INTERHEART study）: case-control study[J]. Lancet, 2004,364（9438）:937-52
[2] 王若琦, 王玉敏. 他汀类药品少见的不良反应[J]. 中国药物警戒, 2009 （2）: 105-108.
[3] Romaine S P, Bailey K M, Hall A S, et al. The influence of SLCO1B1 （OATP1B1） gene polymorphisms on response to statin therapy[J]. Pharmacogenomics J, 2010,10（1）:1-11.
[4] Prado Y, Saavedra N, Zambrano T, et al. SLCO1B1 c.388A>G Polymorphism Is Associated with HDL-C Levels in Response to Atorvastatin in Chilean Individuals[J]. Int J Mol Sci,2015 ,16（9）:20609-19.
[5] Fu Q, Li Y P, Gao Y, et al. Lack of association between SLCO1B1 polymorphism and the lipid-lowering effects of atorvastatin and simvastatin in Chinese individuals[J]. Eur J Clin Pharmacol, 2013,69（6）:1269-74.
[6] Giannakopoulou E, Ragia G, Kolovou V, et al. No impact of SLCO1B1 521T>C, 388A>G and 411G>A polymorphisms on response to statin therapy in the Greek population[J]. Mol Biol Rep, 2014 ,41（7）:4631-8.
[7] 张亚同,梁欣,胡欣,等. 基于连接酶反应快速检测华法林相关基因VKORC1、CYP2C9多态性[J]. 中国临床药理学与治疗学, 2010, 12（12）:1395-1401
[8] Nishizato Y, Ieiri I, Suzuki H, et al. Polymorphisms of OATP‐C （SLC21A6） and OAT3 （SLC22A8） genes: Consequences for pravastatin pharmacokinetics[J]. Clinical Pharmacology & Therapeutics, 2003, 73（6）: 554-565.
[9] Birmingham B K, Bujac S R, Elsby R. Impact of ABCG2 and SLCO1B1 polymorphisms on pharmacokinetics of rosuvastatin, atorvastatin and simvastatin acid in Caucasian and Asian subjects: a class effect?[J]. European journal of clinical pharmacology, 2015, 71（3）: 341-355.
[10] SEARCH Collaborative Group. SLCO1B1 variants and statin-induced myopathy—a genomewide study[J]. N Engl J Med, 2008, 2008（359）: 789-799.
[11] Zhang W, Chen B L, Ozdemir V, et al. SLCO1B1 521T >C functional genetic polymorphism and lipid-lowering efficacy of multiple-dose pravastatin in Chinese coronary heart disease patients[J]. Br J Clin Pharmacol, 2007,64（3）:346-52.
[12] Mwinyi J, Johne A, Bauer S, et al. Evidence for inverse effects of OATP‐C （SLC21A6）* 5 and* 1b haplotypes on pravastatin kinetics[J]. Clinical Pharmacology & Therapeutics, 2004, 75（5）: 415-421.
[13] Donnelly L A, Doney A S, Tavendale R, et al.Common nonsynonymous substitutions in SLCO1B1 predispose to statin intolerance in routinely treated individuals with type 2 diabetes: a go-DARTS study[J]. Clin Pharmacol Ther, 2011, 89（2）:210-6.
[14] Rodrigues AC1, Perin PM, Purim SG, et al.Pharmacogenetics of OATP transporters reveals that SLCO1B1 c.388A>G variant is determinant of increased atorvastatin response[J]. Int J Mol Sci, 2011, 12（9）:5815-27.
[15] Sortica VA1, Fiegenbaum M, Lima LO, et al.SLCO1B1 gene variability influences lipid-lowering efficacy on simvastatin therapy in Southern Brazilians. Clin Chem Lab Med, 2012, 50（3）:441-8.
[16] Wen J, Xiong Y.J .OATP1B1 388A>G polymorphism and pharmacokinetics of pitavastatin in Chinese healthy volunteers. Clin Pharm Ther, 2010, 35（1）:99-104.
[17] Kadam P, Ashavaid T F, Ponde C K, et al.Genetic determinants of lipid-lowering response to atorvastatin therapy in an Indian population. J Clin Pharm Ther, 2016, 41（3）:329-33.
[18] Lee E, Ryan S, Birmingham B, et al. Rosuvastatin pharmacokinetics and pharmacogenetics in white and Asian subjects residing in the same environment[J]. Clinical Pharmacology & Therapeutics, 2005, 78（4）: 330-341.
[19] 付强,李彦鹏. SLCO1B1基因多态性对阿托伐他汀降脂疗效的影响[J]. 中国新药杂志, 2016, （11）:1266-1270.
[20] Pasanen M K, Fredrikson H, Neuvonen P J, et al. Different effects of SLCO1B1 polymorphism on the pharmacokinetics of atorvastatin and rosuvastatin[J]. Clinical Pharmacology & Therapeutics, 2007, 82（6）: 726-733.
[21] Niemi M, Pasanen M K, Neuvonen P J. SLCO1B1 polymorphism and sex affect the pharmacokinetics of pravastatin but not fluvastatin[J]. Clinical Pharmacology & Therapeutics, 2006, 80（4）: 356-366.