Pharmacogenetics of statins: achievements, whole-genome analyses and future perspectives

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

References

• 1  McGovern PG, Pankow JS, Shahar E et al. Recent trends in acute coronary heart disease – mortality, morbidity, medical care, and risk factors. The Minnesota heart survey investigators. N. Engl. J. Med.334(14),884–890 (1996).
  Medline CASGoogle Scholar
• 2  Davidson MH, Toth PP. Comparative effects of lipid-lowering therapies. Prog. Cardiovasc. Dis.47(2),73–104 (2004).
  Medline CASGoogle Scholar
• 3  Ballantyne CM. Achieving greater reductions in cardiovascular risk: lessons from statin therapy on risk measures and risk reduction. Am. Heart J.148(Suppl. 1),S3–S8 (2004).
  Medline CASGoogle Scholar
• 4  Shepherd J, Blauw GJ, Murphy MB et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet360(9346),1623–1630 (2002).
  Medline CASGoogle Scholar
• 5  Schmitz G, Langmann T. Pharmacogenomics of cholesterol-lowering therapy. Vascul. Pharmacol.44(2),75–89 (2006).▪ An elaborate overview of 33 published pharmacogenetic candidate genes and their genotype effects related to statin therapy.
  Medline CASGoogle Scholar
• 6  Verschuren JJ, Trompet S, Wessels JA et al. A systematic review on pharmacogenetics in cardiovascular disease: is it ready for clinical application? Eur. Heart J.33(2),165–175 (2012).▪ A comprehensive overview of the current knowledge on pharmacogenetics of all major drug classes used in the treatment of cardiovascular diseases.
  Medline CASGoogle Scholar
• 7  Chasman DI, Posada D, Subrahmanyan L, Cook NR, Stanton VP Jr, Ridker PM. Pharmacogenetic study of statin therapy and cholesterol reduction. JAMA291(23),2821–2827 (2004).
  Medline CASGoogle Scholar
• 8  Nieminen T, Kahonen M, Viiri LE, Gronroos P, Lehtimaki T. Pharmacogenetics of apolipoprotein E gene during lipid-lowering therapy: lipid levels and prevention of coronary heart disease. Pharmacogenomics9(10),1475–1486 (2008).▪▪ A summary of the pharmacogenetic findings related to the influence of APOE gene variation on statin effects.
  CASGoogle Scholar
• 9  Lehtimaki T, Moilanen T, Viikari J et al. Apolipoprotein E phenotypes in Finnish youths: a cross-sectional and 6 year follow-up study. J. Lipid Res.31(3),487–495 (1990).
  Medline CASGoogle Scholar
• 10  Lehtimaki T, Moilanen T, Nikkari T et al. Regional differences in apolipoprotein E polymorphism in Finland. Ann. Med.23(1),61–66 (1991).
  Medline CASGoogle Scholar
• 11  Ilveskoski E, Loimaala A, Mercuri MF et al. Apolipoprotein E polymorphism and carotid artery intima–media thickness in a random sample of middle-aged men. Atherosclerosis153(1),147–153 (2000).
  Medline CASGoogle Scholar
• 12  Zintzaras E, Kitsios GD, Triposkiadis F, Lau J, Raman G. APOE gene polymorphisms and response to statin therapy. Pharmacogenomics J.9(4),248–257 (2009).
  Medline CASGoogle Scholar
• 13  Kajinami K, Takekoshi N, Brousseau ME, Schaefer EJ. Pharmacogenetics of HMG-CoA reductase inhibitors: exploring the potential for genotype-based individualization of coronary heart disease management. Atherosclerosis177(2),219–234 (2004).
  Medline CASGoogle Scholar
• 14  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.84(4),457–461 (2008).
  Medline CASGoogle Scholar
• 15  Romaine SP, Bailey KM, Hall AS, Balmforth AJ. The influence of SLCO1B1 (OATP1B1) gene polymorphisms on response to statin therapy. Pharmacogenomics J.10(1),1–11 (2010).
  Medline CASGoogle Scholar
• 16  Mangravite LM, Thorn CF, Krauss RM. Clinical implications of pharmacogenomics of statin treatment. Pharmacogenomics J.6(6),360–374 (2006).
  Medline CASGoogle Scholar
• 17  Assimes TL, Holm H, Kathiresan S et al. Lack of association between the Trp719Arg polymorphism in kinesin-like protein-6 and coronary artery disease in 19 case–control studies. J. Am. Coll. Cardiol.56(19),1552–1563 (2010).
  Medline CASGoogle Scholar
• 18  Iakoubova OA, Sabatine MS, Rowland CM et al. Polymorphism in KIF6 gene and benefit from statins after acute coronary syndromes: results from the PROVE IT-TIMI 22 study. J. Am. Coll. Cardiol.51(4),449–455 (2008).
  Medline CASGoogle Scholar
• 19  Iakoubova OA, Tong CH, Rowland CM et al. Association of the Trp719Arg polymorphism in kinesin-like protein 6 with myocardial infarction and coronary heart disease in 2 prospective trials: the CARE and WOSCOPS trials. J. Am. Coll. Cardiol.51(4),435–443 (2008).
  Medline CASGoogle Scholar
• 20  Li Y, Iakoubova OA, Shiffman D, Devlin JJ, Forrester JS, Superko HR. KIF6 polymorphism as a predictor of risk of coronary events and of clinical event reduction by statin therapy. Am. J. Cardiol.106(7),994–998 (2010).
  Medline CASGoogle Scholar
• 21  Shiffman D, Chasman DI, Zee RY et al. A kinesin family member 6 variant is associated with coronary heart disease in the Women’s Health Study. J. Am. Coll. Cardiol.51(4),444–448 (2008).
  Medline CASGoogle Scholar
• 22  Bare LA, Morrison AC, Rowland CM et al. Five common gene variants identify elevated genetic risk for coronary heart disease. Genet. Med.9(10),682–689 (2007).
  Medline CASGoogle Scholar
• 23  Shiffman D, O’Meara ES, Bare LA et al. Association of gene variants with incident myocardial infarction in the Cardiovascular health study. Arterioscler. Thromb. Vasc. Biol.28(1),173–179 (2008).
  Medline CASGoogle Scholar
• 24  Iakoubova OA, Robertson M, Tong CH et al.KIF6 Trp719Arg polymorphism and the effect of statin therapy in elderly patients: results from the PROSPER study. Eur. J. Cardiovasc. Prev. Rehabil.17(4),455–461 (2010).
  MedlineGoogle Scholar
• 25  Marian AJ. Surprises of the genome and “personalized” medicine. J. Am. Coll. Cardiol.51(4),456–458 (2008).
  MedlineGoogle Scholar
• 26  Hopewell JC, Parish S, Clarke R et al. No impact of KIF6 genotype on vascular risk and statin response among 18,348 randomized patients in the heart protection study. J. Am. Coll. Cardiol.57(20),2000–2007 (2011).
  Medline CASGoogle Scholar
• 27  Maggo SD, Kennedy MA, Clark DW. Clinical implications of pharmacogenetic variation on the effects of statins. Drug Saf.34(1),1–19 (2011).
  Medline CASGoogle Scholar
• 28  Kuivenhoven JA, de Knijff P, Boer JM et al. Heterogeneity at the CETP gene locus. Influence on plasma CETP concentrations and HDL cholesterol levels. Arterioscler. Thromb. Vasc. Biol.17(3),560–568 (1997).
  Medline CASGoogle Scholar
• 29  Kuivenhoven JA, Jukema JW, Zwinderman AH et al. 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.338(2),86–93 (1998).
  Medline CASGoogle Scholar
• 30  Freeman DJ, Samani NJ, Wilson V et al. A polymorphism of the cholesteryl ester transfer protein gene predicts cardiovascular events in non-smokers in the West of Scotland coronary prevention study. Eur. Heart J.24(20),1833–1842 (2003).
  Medline CASGoogle Scholar
• 31  Ordovas JM, Cupples LA, Corella D et al. Association of cholesteryl ester transfer protein-TaqIB polymorphism with variations in lipoprotein subclasses and coronary heart disease risk: the Framingham study. Arterioscler. Thromb. Vasc. Biol.20(5),1323–1329 (2000).
  Medline CASGoogle Scholar
• 32  Liu S, Schmitz C, Stampfer MJ et al. A prospective study of TaqIB polymorphism in the gene coding for cholesteryl ester transfer protein and risk of myocardial infarction in middle-aged men. Atherosclerosis161(2),469–474 (2002).
  Medline CASGoogle Scholar
• 33  Jukema JW, Bruschke AV, van Boven AJ et al. Effects of lipid lowering by pravastatin on progression and regression of coronary artery disease in symptomatic men with normal to moderately elevated serum cholesterol levels. The regression growth evaluation statin study (REGRESS). Circulation91(10),2528–2540 (1995).
  Medline CASGoogle Scholar
• 34  Regieli JJ, Jukema JW, Grobbee DE et al.CETP genotype predicts increased mortality in statin-treated men with proven cardiovascular disease: an adverse pharmacogenetic interaction. Eur. Heart J.29(22),2792–2799 (2008).
  Medline CASGoogle Scholar
• 35  Boekholdt SM, Sacks FM, Jukema JW 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. Circulation111(3),278–287 (2005).
  Medline CASGoogle Scholar
• 36  Gerdes LU, Gerdes C, Kervinen K et al. The apolipoprotein ε4 allele determines prognosis and the effect on prognosis of simvastatin in survivors of myocardial infarction: a substudy of the Scandinavian simvastatin survival study. Circulation101(12),1366–1371 (2000).
  Medline CASGoogle Scholar
• 37  Maitland-van der Zee AH, Jukema JW, Zwinderman AH et al. Apolipoprotein-E polymorphism and response to pravastatin in men with coronary artery disease (REGRESS). Acta Cardiol.61(3),327–331 (2006).
  MedlineGoogle Scholar
• 38  Maitland-van der Zee AH, Stricker BH, Klungel OH et al. The effectiveness of hydroxy-methylglutaryl coenzyme A reductase inhibitors (statins) in the elderly is not influenced by apolipoprotein E genotype. Pharmacogenetics12(8),647–653 (2002).
  Medline CASGoogle Scholar
• 39  Peters BJ, Rodin AS, Klungel OH et al. Pharmacogenetic interactions between ABCB1 and SLCO1B1 tagging SNPs and the effectiveness of statins in the prevention of myocardial infarction. Pharmacogenomics11(8),1065–1076 (2010).
  CASGoogle Scholar
• 40  Thompson JF, Hyde CL, Wood LS et al. Comprehensive whole-genome and candidate gene analysis for response to statin therapy in the Treating to New Targets (TNT) cohort. Circ. Cardiovasc. Genet.2(2),173–181 (2009).▪▪ Genome-wide association (GWA) analysis of lipid-lowering response to statins in the TNT cohort.
  Medline CASGoogle Scholar
• 41  Link E, Parish S, Armitage J et al.SLCO1B1 variants and statin-induced myopathy – a genomewide study. N. Engl. J. Med.359(8),789–799 (2008).▪▪ GWA study showing a strong association between SLCO1B1 variants and statin-induced myopathy.
  Medline CASGoogle Scholar
• 42  Barber MJ, Mangravite LM, Hyde CL et al. Genome-wide association of lipid-lowering response to statins in combined study populations. PLoS ONE5(3),e9763 (2010).▪▪ GWA analysis of lipid-lowering response to statins in the CAP, PRINCE and TNT trials.
  MedlineGoogle Scholar
• 43  Brunham LR, Lansberg PJ, Zhang L et al. Differential effect of the rs4149056 variant in SLCO1B1 on myopathy associated with simvastatin and atorvastatin. Pharmacogenomics J. doi:10.1038/tpj.2010.92 (2011) (Epub ahead of print).
  MedlineGoogle Scholar
• 44  Trompet S, de Craen AJ, Postmus I et al. Replication of LDL GWAs hits in PROSPER/PHASE as validation for future (pharmaco)genetic analyses. BMC Med. Genet.12(1),131 (2011).▪ A description of the methods and a proof-of-principle analysis performed in the PROSPER/PHASE study.
  Medline CASGoogle Scholar
• 45  Colhoun HM, Thomason MJ, Mackness MI et al. Design of the collaborative AtoRvastatin Diabetes Study (CARDS) in patients with Type 2 diabetes. Diabet. Med.19(3),201–211 (2002).
  Medline CASGoogle Scholar
• 46  Sever PS, Dahlof B, Poulter NR et al. Rationale, design, methods and baseline demography of participants of the Anglo–Scandinavian cardiac outcomes trial. ASCOT investigators. J. Hypertens.19(6),1139–1147 (2001).
  Medline CASGoogle Scholar
• 47  Psaty BM, O’Donnell CJ, Gudnason V et al. Cohorts for heart and aging research in genomic epidemiology (CHARGE) consortium: design of prospective meta-analyses of genome-wide association studies from 5 cohorts. Circ. Cardiovasc. Genet.2(1),73–80 (2009).
  MedlineGoogle Scholar
• 48  Bild DE, Bluemke DA, Burke GL et al. Multi-ethnic study of atherosclerosis: objectives and design. Am. J. Epidemiol.156(9),871–881 (2002).
  MedlineGoogle Scholar
• 49  Yende S, Waterer GW, Tolley EA et al. Inflammatory markers are associated with ventilatory limitation and muscle dysfunction in obstructive lung disease in well functioning elderly subjects. Thorax61(1),10–16 (2006).
  Medline CASGoogle Scholar
• 50  Psaty BM, Heckbert SR, Koepsell TD et al. The risk of myocardial infarction associated with antihypertensive drug therapies. JAMA274(8),620–625 (1995).
  Medline CASGoogle Scholar
• 51  Pearson ER, Donnelly LA, Kimber C et al. Variation in TCF7L2 influences therapeutic response to sulfonylureas: a GoDARTs study. Diabetes56(8),2178–2182 (2007).
  Medline CASGoogle Scholar
• 52  Wilke RA. High-density lipoprotein (HDL) cholesterol: leveraging practice-based biobank cohorts to characterize clinical and genetic predictors of treatment outcome. Pharmacogenomics J.11(3),162–173 (2011).
  Medline CASGoogle Scholar
• 53  Seo D, Ginsburg GS, Goldschmidt-Clermont PJ. Gene expression analysis of cardiovascular diseases: novel insights into biology and clinical applications. J. Am. Coll. Cardiol.48(2),227–235 (2006).
  Medline CASGoogle Scholar
• 54  Meisel C, Gerloff T, Kirchheiner J et al. Implications of pharmacogenetics for individualizing drug treatment and for study design. J. Mol. Med. (Berl.)81(3),154–167 (2003).
  MedlineGoogle Scholar
• 55  McDonagh EM, Whirl-Carrillo M, Garten Y, Altman RB, Klein TE. From pharmacogenomic knowledge acquisition to clinical applications: the PharmGKB as a clinical pharmacogenomic biomarker resource. Biomark. Med.5(6),795–806 (2011).
  CASGoogle Scholar
• 56  Krauss RM, Mangravite LM, Smith JD et al. 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. Circulation117(12),1537–1544 (2008).
  Medline CASGoogle Scholar
• 57  Carlquist JF, Muhlestein JB, Horne BD et al. The cholesteryl ester transfer protein Taq1B gene polymorphism predicts clinical benefit of statin therapy in patients with significant coronary artery disease. Am. Heart J.146(6),1007–1014 (2003).
  Medline CASGoogle Scholar