Pharmacogenomics Statins: Biomarkers for Clinical Prediction

Herni Suprapti

Abstract


Statins are the most widely prescribed drug for hyperlipidemic therapy and for the prevention of Cardiovascular disease. But although statins are very effective for the prevention of atherosclerosis, there are still patients with CVD. In this case, it is thought to be the influence of genetic factors. There is a static gene link to statin dose required for therapy, but there are still no relevant pharmacogenomic tests for statin therapy guidelines. This article describes basic pharmacogenomic terminology, genes (CETP, HMGCR, SLCO1B1, ABCB1, and CYP3A4 / 5), and progression of statin pharmacogenomic biomarkers for predicted therapeutic outcomes.


Keywords


statin; biomarker; farmacogenomic

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Kitzmiller JP, Binkley PF, Pandey SR, Suhy AM, Baldassarre D, Hartmann K. Statin Pharmacogenomics: Pursuing Biomarkers for Predicting Clinical Outcomes Discov Med. 2013 August ; 16(86): 45–51.

Gaziano TA, Bitton A, Anand S, Abrahams-Gessel S, Murphy A. Growing epidemic of coronary heart disease in low- and middle-income countries. Curr Probl Cardiol. 2010; 35(2):72–115. [PubMed: 20109979]

Amarenco P, Labreuche J. Lipid management in the prevention of stroke: review and updated meta-analysis of statins for stroke prevention. Lancet Neurol. 2009; 8(5):453–463. [PubMed: 19375663]

IMS Institute for Healthcare Informatics. [Accessed Jul. 1, 2013] Declining Medicine Use and Costs: For Better or Worse?. A Review of the Use of Medicines in the United States in 2012. 2013. from http://www.imshealth.com.)

Freeman DJ, Griffin BA, Holmes AP, Lindsay GM, Gaffney D, Packard CJ, Shepherd J. Regulation of plasma HDL cholesterol and subfraction distribution by genetic and environmental factors. Associations between the TaqI B RFLP in the CETP gene and smoking and obesity. Arterioscler Thromb. 1994; 14(3):336–344. [PubMed: 7907227]

Kuivenhoven JA, Jukema JW, Zwinderman AH, de Knijff P, McPherson R, Bruschke AV, Lie KI, Kastelein JJ. The role of a common variant of the cholesteryl ester transfer protein gene in the progression of coronary atherosclerosis. The Regression Growth Evaluation Statin Study Group. N Engl J Med. 1998; 338(2):86–93. [PubMed: 9420339]

Willer CJ, Sanna S, Jackson AU, Scuteri A, Bonnycastle LL, Clarke R, Heath SC, Timpson NJ, Najjar SS, Stringham HM. Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet. 2008; 40(2):161–169. [PubMed: 18193043]

Regieli JJ, Jukema JW, Grobbee DE, Kastelein JJ, Kuivenhoven JA, Zwinderman AH, van der Graaf Y, Bots ML, Doevendans PA. CETP genotype predicts increased mortality in statin-treated men with proven cardiovascular disease: an adverse pharmacogenetic interaction. Eur Heart J. 2008; 29(22):2792–2799. [PubMed: 18957472]

Boekholdt SM, Sacks FM, Jukema JW, Shepherd J, Freeman DJ, McMahon AD, Cambien F, Nicaud V, de Grooth GJ, Talmud PJ, Humphries SE, Miller GJ, Eiriksdottir G, Gudnason V, Kauma H, Kakko S, Savolainen MJ, Arca M, Montali A, Liu S, et al. Cholesteryl ester transfer protein TaqIB variant, high-density lipoprotein cholesterol levels, cardiovascular risk, and efficacy of pravastatin treatment: individual patient meta-analysis of 13,677 subjects. Circulation. 2005; 111(3):278–287. [PubMed: 15655129]

Papp AC, Pinsonneault JK, Wang D, Newman LC, Gong Y, Johnson JA, Pepine CJ, Kumari M, Hingorani AD, Talmud PJ. Cholesteryl Ester Transfer Protein (CETP) polymorphisms affect mRNA splicing, HDL levels, and sex-dependent cardiovascular risk. PLoS One. 2012; 7(3):e31930. [PubMed: 22403620]

Krauss RM, Mangravite LM, Smith JD, Medina MW, Wang D, Guo X, Rieder MJ, Simon JA, Hulley SB, Waters D, Saad M, Williams PT, Taylor KD, Yang H, Nickerson DA, Rotter JI. Variation in the 3-hydroxyl-3-methylglutaryl coenzyme a reductase gene is associated with racial differences in low-density lipoprotein cholesterol response to simvastatin treatment. Circulation. 2008; 117(12): 1537–1544. [PubMed: 18332269]

Chasman DI, Posada D, Subrahmanyan L, Cook NR, Stanton VP Jr, Ridker PM. Pharmacogenetic study of statin therapy and cholesterol reduction. JAMA. 2004; 291(23):2821–2827. [PubMed: 15199031]

Donnelly L, Doney A, Tavendale R, Lang C, Pearson E, Colhoun H, McCarthy M, Hattersley A, Morris A, Palmer C. Common nonsynonymous substitutions in SLCO1B1 predispose to statin intolerance in routinely treated individuals with type 2 diabetes: a go-DARTS study. Clin Pharmacol Ther. 2010; 89(2):210–216. [PubMed: 21178985]

Thompson J, Man M, Johnson K, Wood L, Lira M, Lloyd D, Banerjee P, Milos P, Myrand S, Paulauskis J. An association study of 43 SNPs in 16 candidate genes with atorvastatin response. Pharmacogenomics J. 2005; 5(6):352–358. [PubMed: 16103896]

Singer JB, Holdaas H, Jardine AG, Fellstrøm B, Os I, Bermann G, Meyer JM. Genetic analysis of fluvastatin response and dyslipidemia in renal transplant recipients. J Lipid Res. 2007; 48(9): 2072–2078. [PubMed: 17563401]

Polisecki E, Muallem H, Maeda N, Peter I, Robertson M, McMahon AD, Ford I, Packard C, Shepherd J, Jukema JW. Genetic variation at the LDL receptor and HMG-CoA reductase gene loci, lipid levels, statin response, and cardiovascular disease incidence in PROSPER. Atherosclerosis. 2008; 200(1):109–114. [PubMed: 18261733]

Thompson JF, Hyde CL, Wood LS, Paciga SA, Hinds DA, Cox DR, Hovingh GK, Kastelein JJ. Comprehensive whole-genome and candidate gene analysis for response to statin therapy in the Treating to New Targets (TNT) cohort. Circulation: Cardiovasc Genet. 2009; 2(2):173–181.

Mammen AL, Chung T, Christopher-Stine L, Rosen P, Rosen A, Doering KR, Casciola-Rosen LA. Autoantibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase in patients with statinassociated autoimmune myopathy. Arthritis Rheum. 2011; 63(3):713–721. [PubMed: 21360500]

Werner JL, Christopher-Stine L, Ghazarian SR, Pak KS, Kus JE, Daya NR, Lloyd TE, Mammen AL. Antibody levels correlate with creatine kinase levels and strength in anti-3-hydroxy-3methylglutaryl-coenzyme A reductase-associated autoimmune myopathy. Arthritis Rheum. 2012; 64(12):4087–4093. [PubMed: 22933019]

Peters BJ, Rodin AS, Klungel OH, van Duijn CM, Stricker BHC, van’t Slot R, de Boer A, Maitlandvan der Zee AH. Pharmacogenetic interactions between ABCB1 and SLCO1B1 tagging SNPs and the effectiveness of statins in the prevention of myocardial infarction. Pharmacogenomics. 2010; 11(8):1065–1076. [PubMed: 20712525]

Yang GP, Yuan H, Tang B, Zhang W, Wang LS, Huang ZJ, Ou-Yang DS, Zhang GX, Zhou HH. Lack of effect of genetic polymorphisms of SLCO1B1 on the lipid-lowering response to pitavastatin in Chinese patients. Acta Pharmacol Sin. 2010; 31(3):382–386. [PubMed: 20140004]

Niemi M, Schaeffeler E, Lang T, Fromm MF, Neuvonen M, Kyrklund C, Backman JT, Kerb R, Schwab M, Neuvonen PJ. High plasma pravastatin concentrations are associated with single nucleotide polymorphisms and haplotypes of organic anion transporting polypeptide-C (OATP-C, SLCO1B1). Pharmacogenetics. 2004; 14(7):429–440. [PubMed: 15226675]

Donnelly LA, Doney AS, Dannfald J, Whitley AL, Lang CC, Morris AD, Donnan PT, Palmer CN. A paucimorphic variant in the HMG-CoA reductase gene is associated with lipid-lowering response to statin treatment in diabetes: a GoDARTS study. Pharmacogenetics Genomics. 2008; 18(12):1021– 1026. [PubMed: 18815589]

Link E, Parish S, Armitage J, Bowman L, Heath S, Matsuda F, Gut I, Lathrop M, Collins R. SLCO1B1 variants and statin-induced myopathy — a genome wide study. N Engl J Med. 2008; 359(8):789. [PubMed: 18650507]

Brunham LR, Lansberg PJ, Zhang L, Miao F, Carter C, Hovingh GK, Visscher H, Jukema JW, Stalenhoef AF, Ross CJ, Carleton BC, Kastelein JJ, Hayden MR. Differential effect of the rs4149056 variant in SLCO1B1 on myopathy associated with simvastatin and atorvastatin. Pharmacogenomics J. 2012; 12(3):233–237. [PubMed: 21243006]

Wang D, Johnson AD, Papp AC, Kroetz DL, Sadee W. Multidrug resistance polypeptide 1 (MDR1, ABCB1) variant 3435C> T affects mRNA stability. Pharmacogenetics. 2005; 15(10):693–704.

Keskitalo JE, Kurkinen KJ, Neuvoneni PJ, Niemi M. ABCB1 haplotypes differentially affect the pharmacokinetics of the acid and lactone forms of simvastatin and atorvastatin. Clin Pharmacol Ther. 2008; 84(4):457–461. [PubMed: 19238649]

Sim, SC. [Accessed Jul. 1, 2013] Allele Nomenclature for Cytochrome P450 Enzymes. The Human Cytochrome P450 (CYP) Allele Nomenclature Database. 2011. from http://cypalleles.ki.se.)

Wang D, Guo Y, Wrighton S, Cooke G, Sadee W. Intronic polymorphism in CYP3A4 affects hepatic expression and response to statin drugs. Pharmacogenomics J. 2011; 11(4):274–286. [PubMed: 20386561]

Elens L, Becker ML, Haufroid V, Hofman A, Visser LE, Uitterlinden AG, Stricker BC, van Schaik RH. Novel CYP3A4 intron 6 single nucleotide polymorphism is associated with simvastatinmediated cholesterol reduction in the Rotterdam Study. Pharmacogenetics Genomics. 2011; 21(12): 861–866. [PubMed: 21946898]

Park JE, Kim KB, Bae S, Moon BS, Liu KH, Shin JG. Contribution of cytochrome P450 3A4 and 3A5 to the metabolism of atorvastatin. Xenobiotica. 2008; 38(9):1240–1251. [PubMed: 18720283]

Kim KA, Park PW, Lee OJ, Kang DK, Park JY. Effect of polymorphic CYP3A5 genotype on the single-dose simvastatin pharmacokinetics in healthy subjects. J Clin Pharmacol. 2007; 47(1):87–93. [PubMed: 17192506]

Kivistö KT, Niemi M, Schaeffeler E, Pitkälä K, Tilvis R, Fromm MF, Schwab M, Eichelbaum M, Strandberg T. Lipid-lowering response to statins is affected by CYP3A5 polymorphism. Pharmacogenetics Genomics. 2004; 14(8):523–525.

Shin J, Pauly DF, Pacanowski MA, Langaee T, Frye RF, Johnson JA. Effect of cytochrome P450 3A5 genotype on atorvastatin pharmacokinetics and its interaction with clarithromycin. Pharmacotherapy. 2011; 31(10):942–950. [PubMed: 21950641]

Willrich MAV, Hirata MH, Genvigir FD, Arazi SS, Rebecchi IM, Rodrigues AC, Bernik M, Dorea EL, Bertolami MC, Faludi AA. CYP3A53A allele is associated with reduced lowering-lipid response to atorvastatin in individuals with hypercholesterolemia. Clin Chim Acta. 2008; 398(1): 15–20. [PubMed: 18727922]

Fiegenbaum M, da Silveira FR, van der Sand CR, van der Sand LC, Ferreira ME, Pires RC, Hutz MH. The role of common variants of ABCB1, CYP3A4, and CYP3A5 genes in lipid-lowering efficacy and safety of simvastatin treatment. Clin Pharmacol Ther. 2005; 78(5):551–558. [PubMed: 16321621]

Squibb, Bristol-Myers. Coumadin (warfarin sodium). Prescribing Information. 2010

Pendergrass S, Brown-Gentry K, Dudek S, Torstenson E, Ambite J, Avery C, Buyske S, Cai C, Fesinmeyer M, Haiman C. The use of phenome-wide association studies (PheWAS) for exploration of novel genotype-phenotype relationships and pleiotropy discovery. Genet Epidemiol. 2011; 35(5):410–422. [PubMed: 21594894]




DOI: http://dx.doi.org/10.30742/jikw.v7i1.61

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