Statins Personalized

Medical Clinics of North America

Volumn 96, Issue 1, 2012, Pages 123-139

  Superko, H Robert ^a,b,c   Momary, Kathryn M ^b   Li, Yonghong ^a  

^a CELERA   (United States)

^b MERCER UNIVERSITY   (United States)

^c Saint Joseph's Hospital of Atlanta   (United States)

Author keywords

Cholesterol; Coronary heart disease; Genetic; Polymorphism; Statin

Indexed keywords

ATORVASTATIN; BILE ACID; CERIVASTATIN; CHOLESTEROL ACYLTRANSFERASE; FLUINDOSTATIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LIPOPROTEIN LIPASE; LIVER TRIACYLGLYCEROL LIPASE; LOW DENSITY LIPOPROTEIN CHOLESTEROL; MEVINOLIN; PHOSPHATIDYLCHOLINE STEROL ACYLTRANSFERASE; PRAVASTATIN; ROSUVASTATIN; SIMVASTATIN; STEROID HORMONE;

BILE ACID METABOLISM; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CHOLESTEROL METABOLISM; CHOLESTEROL SYNTHESIS; DRUG HYPERSENSITIVITY; ENVIRONMENTAL FACTOR; ENZYME ACTIVITY; ESTERIFICATION; GENETIC ASSOCIATION; GENETIC VARIABILITY; HOMEOSTASIS; HUMAN; HYDROLYSIS; LIPID BLOOD LEVEL; LIPID METABOLISM; LIVER CELL; MYALGIA; MYOPATHY; PHARMACOGENETICS; PHENOTYPE; PRIORITY JOURNAL; REVIEW; RHABDOMYOLYSIS; SINGLE NUCLEOTIDE POLYMORPHISM; TRANSCRIPTION REGULATION; TREATMENT RESPONSE;

CHOLESTEROL, LDL; DRUG RESISTANCE; DYSLIPIDEMIAS; FORECASTING; GENE-ENVIRONMENT INTERACTION; HUMANS; HYDROXYMETHYLGLUTARYL COA REDUCTASES; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; INDIVIDUALIZED MEDICINE; LIPID METABOLISM; PATIENT COMPLIANCE; PHARMACOGENETICS; POLYMORPHISM, SINGLE NUCLEOTIDE;

EID: 84863229143     PISSN: 00257125     EISSN: 15579859     Source Type: Journal    
DOI: 10.1016/j.mcna.2011.11.004     Document Type: Review

References (90)

1. National Center for Health Statistics. Health, United States, 2010: with special feature on death and dying. Hyattsville (MD); 2011.
2. Superko H.R., King S. Lipid management to reduce cardiovascular risk: a new strategy is required. Circulation 2008, 117(4):560-568. [discussion: 8].
3. Goldstein J.L., Brown M.S. Regulation of the mevalonate pathway. Nature 1990, 343(6257):425-430.
4. Hamon Y., Broccardo C., Chambenoit O., et al. ABC1 promotes engulfment of apoptotic cells and transbilayer redistribution of phosphatidylserine. Nat Cell Biol 2000, 2(7):399-406.
5. Mahley R.W., Innerarity T.L., Rall S.C., et al. Plasma lipoproteins: apolipoprotein structure and function. J Lipid Res 1984, 25(12):1277-1294.
6. Mahley R.W., Innerarity T.L., Rall S.C., et al. Lipoproteins of special significance in atherosclerosis. Insights provided by studies of type III hyperlipoproteinemia. Ann N Y Acad Sci 1985, 454:209-221.
7. Heller D.A., de Faire U., Pedersen N.L., et al. Genetic and environmental influences on serum lipid levels in twins. N Engl J Med 1993, 328(16):1150-1156.
8. Hobbs H.H., Brown M.S., Goldstein J.L. Molecular genetics of the LDL receptor gene in familial hypercholesterolemia. Hum Mutat 1992, 1(6):445-466.
9. Teslovich T.M., Musunuru K., Smith A.V., et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature 2010, 466(7307):707-713.
10. Hegele R.A. Plasma lipoproteins: genetic influences and clinical implications. Nat Rev Genet 2009, 10(2):109-121.
11. Aulchenko Y.S., Ripatti S., Lindqvist I., et al. Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts. Nat Genet 2009, 41(1):47-55.
12. Chasman D.I., Pare G., Mora S., et al. Forty-three loci associated with plasma lipoprotein size, concentration, and cholesterol content in genome-wide analysis. PLoS Genet 2009, 5(11):e1000730.
13. Kathiresan S., Melander O., Guiducci C., et al. Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans. Nat Genet 2008, 40(2):189-197.
14. Kathiresan S., Willer C.J., Peloso G.M., et al. Common variants at 30 loci contribute to polygenic dyslipidemia. Nat Genet 2009, 41(1):56-65.
15. Kooner J.S., Chambers J.C., Aguilar-Salinas C.A., et al. Genome-wide scan identifies variation in MLXIPL associated with plasma triglycerides. Nat Genet 2008, 40(2):149-151.
16. Sabatti C., Service S.K., Hartikainen A.L., et al. Genome-wide association analysis of metabolic traits in a birth cohort from a founder population. Nat Genet 2009, 41(1):35-46.
17. Sandhu M.S., Waterworth D.M., Debenham S.L., et al. LDL-cholesterol concentrations: a genome-wide association study. Lancet 2008, 371(9611):483-491.
18. Wallace C., Newhouse S.J., Braund P., et al. Genome-wide association study identifies genes for biomarkers of cardiovascular disease: serum urate and dyslipidemia. Am J Hum Genet 2008, 82(1):139-149.
19. Willer C.J., Sanna S., Jackson A.U., et al. Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet 2008, 40(2):161-169.
20. Waterworth D.M., Ricketts S.L., Song K., et al. Genetic variants influencing circulating lipid levels and risk of coronary artery disease. Arterioscler Thromb Vasc Biol 2010, 30(11):2264-2276.
21. Mega J.L., Morrow D.A., Brown A., et al. Identification of genetic variants associated with response to statin therapy. Arterioscler Thromb Vasc Biol 2009, 29(9):1310-1315.
22. Bennet A.M., Di Angelantonio E., Ye Z., et al. Association of apolipoprotein E genotypes with lipid levels and coronary risk. JAMA 2007, 298(11):1300-1311.
23. Musunuru K., Strong A., Frank-Kamenetsky M., et al. From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus. Nature 2010, 466(7307):714-719.
24. Manolio T.A., Collins F.S., Cox N.J., et al. Finding the missing heritability of complex diseases. Nature 2009, 461(7265):747-753.
25. Umans-Eckenhausen M.A., Sijbrands E.J., Kastelein J.J., et al. Low-density lipoprotein receptor gene mutations and cardiovascular risk in a large genetic cascade screening population. Circulation 2002, 106(24):3031-3036.
26. Dumitrescu L., Carty C.L., Taylor K., et al. Genetic determinants of lipid traits in diverse populations from the population architecture using genomics and epidemiology (PAGE) study. PLoS Genet 2011, 7(6):e1002138.
27. Smith M.E., Lee N.J., Haney E., et al. Drug class review: HMG-CoA reductase inhibitors (statins) and fixed-dose combination products containing a statin: final report update 5 2009, Oregon Health & Science University, Portland (OR).
28. Sirtori C.R., Mombelli G., Triolo M., et al. Clinical response to statins: Mechanism(s) of variable activity and adverse effects. Ann Med 2011, [Epub ahead of print].
29. Deambrosis P., Saramin C., Terrazzani G., et al. Evaluation of the prescription and utilization patterns of statins in an Italian local health unit during the period 1994-2003. Eur J Clin Pharmacol 2007, 63(2):197-203.
30. Shear C.L., Franklin F.A., Stinnett S., et al. Expanded Clinical Evaluation of Lovastatin (EXCEL) study results. Effect of patient characteristics on lovastatin-induced changes in plasma concentrations of lipids and lipoproteins. Circulation 1992, 85(4):1293-1303.
31. Pedan A., Varasteh L., Schneeweiss S. Analysis of factors associated with statin adherence in a hierarchical model considering physician, pharmacy, patient, and prescription characteristics. J Manag Care Pharm 2007, 13(6):487-496.
32. Perreault S., Blais L., Lamarre D., et al. Persistence and determinants of statin therapy among middle-aged patients for primary and secondary prevention. Br J Clin Pharmacol 2005, 59(5):564-573.
33. Simon J.A., Lin F., Hulley S.B., et al. Phenotypic predictors of response to simvastatin therapy among African-Americans and Caucasians: the Cholesterol and Pharmacogenetics (CAP) Study. Am J Cardiol 2006, 97(6):843-850.
34. Hunt D., Young P., Simes J., et al. Benefits of pravastatin on cardiovascular events and mortality in older patients with coronary heart disease are equal to or exceed those seen in younger patients: Results from the LIPID trial. Ann Intern Med 2001, 134(10):931-940.
35. Lewis S.J., Moye L.A., Sacks F.M., et al. Effect of pravastatin on cardiovascular events in older patients with myocardial infarction and cholesterol levels in the average range. Results of the Cholesterol and Recurrent Events (CARE) trial. Ann Intern Med 1998, 129(9):681-689.
36. Cone C., Murata G., Myers O. Demographic determinants of response to statin medications. Am J Health Syst Pharm 2011, 68(6):511-517.
37. Ose L., Shah A., Davies M.J., et al. Consistency of lipid-altering effects of ezetimibe/simvastatin across gender, race, age, baseline low density lipoprotein cholesterol levels, and coronary heart disease status: results of a pooled retrospective analysis. Curr Med Res Opin 2006, 22(5):823-835.
38. Gupta M., Braga M.F., Teoh H., et al. Statin effects on LDL and HDL cholesterol in South Asian and white populations. J Clin Pharmacol 2009, 49(7):831-837.
39. de Sauvage Nolting P.R., Buirma R.J., Hutten B.A., et al. Baseline lipid values partly determine the response to high-dose simvastatin in patients with familial hypercholesterolemia. The examination of probands and relatives in Statin studies with familial hypercholesterolemia (ExPRESS FH). Atherosclerosis 2002, 164(2):347-354.
40. Streja L., Packard C.J., Shepherd J., et al. Factors affecting low-density lipoprotein and high-density lipoprotein cholesterol response to pravastatin in the West Of Scotland Coronary Prevention Study (WOSCOPS). Am J Cardiol 2002, 90(7):731-736.
41. Nakajima K. Sex-related differences in response of plasma lipids to simvastatin: the Saitama Postmenopausal Lipid Intervention Study. S-POLIS Group. Clin Ther 1999, 21(12):2047-2057.
42. Kannel W.B., D'Agostino R.B., Stepanians M., et al. Efficacy and tolerability of lovastatin in a six-month study: analysis by gender, age and hypertensive status. Am J Cardiol 1990, 66(8):1B-10B.
43. Thompson J.F., Hyde C.L., Wood L.S., 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 2009, 2:173-181.
44. Barber M.J., Mangravite L.M., Hyde C.L., et al. Genome-wide association of lipid-lowering response to statins in combined study populations. PLoS One 2010, 5(3):e9763.
45. Voora D., Shah S.H., Reed C.R., et al. Pharmacogenetic predictors of statin-mediated low-density lipoprotein cholesterol reduction and dose response. Circ Cardiovasc Genet 2008, 1:100-106.
46. Ballantyne C.M., Herd J.A., Stein E.A., et al. Apolipoprotein E genotypes and response of plasma lipids and progression-regression of coronary atherosclerosis to lipid-lowering drug therapy. J Am Coll Cardiol 2000, 36(5):1572-1578.
47. Baptista R., Rebelo M., Decq-Mota J., et al. Apolipoprotein E epsilon-4 polymorphism is associated with younger age at referral to a lipidology clinic and a poorer response to lipid-lowering therapy. Lipids Health Dis 2011, 10:48.
48. Donnelly L.A., Palmer C.N., Whitley A.L., et al. Apolipoprotein E genotypes are associated with lipid-lowering responses to statin treatment in diabetes: a Go-DARTS study. Pharmacogenet Genomics 2008, 18(4):279-287.
49. Thompson J.F., Man M., Johnson K.J., et al. An association study of 43 SNPs in 16 candidate genes with atorvastatin response. Pharmacogenomics J 2005, 5(6):352-358.
50. Zintzaras E., Kitsios G.D., Triposkiadis F., et al. APOE gene polymorphisms and response to statin therapy. Pharmacogenomics J 2009, 9(4):248-257.
51. Chasman D.I., Posada D., Subrahmanyan L., et al. Pharmacogenetic study of statin therapy and cholesterol reduction. JAMA 2004, 291(23):2821-2827.
52. Krauss R.M., Mangravite L.M., Smith J.D., 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. Circulation 2008, 117(12):1537-1544.
53. Polisecki E., Muallem H., Maeda N., et al. 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.
54. Singer J.B., Holdaas H., Jardine A.G., et al. Genetic analysis of fluvastatin response and dyslipidemia in renal transplant recipients. J Lipid Res 2007, 48(9):2072-2078.
55. Chien K.L., Wang K.C., Chen Y.C., et al. Common sequence variants in pharmacodynamic and pharmacokinetic pathway-related genes conferring LDL cholesterol response to statins. Pharmacogenomics 2010, 11(3):309-317.
56. Burkhardt R., Kenny E.E., Lowe J.K., et al. Common SNPs in HMGCR in micronesians and whites associated with LDL-cholesterol levels affect alternative splicing of exon13. Arterioscler Thromb Vasc Biol 2008, 28(11):2078-2084.
57. Medina M.W., Gao F., Ruan W., et al. Alternative splicing of 3-hydroxy-3-methylglutaryl coenzyme A reductase is associated with plasma low-density lipoprotein cholesterol response to simvastatin. Circulation 2008, 118(4):355-362.
58. Romaine S.P., Bailey K.M., Hall A.S., et al. The influence of SLCO1B1 (OATP1B1) gene polymorphisms on response to statin therapy. Pharmacogenomics J 2010, 10(1):1-11.
59. Tirona R.G., Leake B.F., Merino G., et al. Polymorphisms in OATP-C: identification of multiple allelic variants associated with altered transport activity among European- and African-Americans. J Biol Chem 2001, 276(38):35669-35675.
60. Pasanen M.K., Fredrikson H., Neuvonen P.J., et al. Different effects of SLCO1B1 polymorphism on the pharmacokinetics of atorvastatin and rosuvastatin. Clin Pharmacol Ther 2007, 82(6):726-733.
61. Pasanen M.K., Neuvonen M., Neuvonen P.J., et al. SLCO1B1 polymorphism markedly affects the pharmacokinetics of simvastatin acid. Pharmacogenet Genomics 2006, 16(12):873-879.
62. Niemi M., Pasanen M.K., Neuvonen P.J. SLCO1B1 polymorphism and sex affect the pharmacokinetics of pravastatin but not fluvastatin. Clin Pharmacol Ther 2006, 80(4):356-366.
63. Link E., Parish S., Armitage J., et al. SLCO1B1 variants and statin-induced myopathy-a genomewide study. N Engl J Med 2008, 359(8):789-799.
64. Wang C.Y., Liu P.Y., Liao J.K. Pleiotropic effects of statin therapy: molecular mechanisms and clinical results. Trends Mol Med 2008, 14(1):37-44.
65. Hindorff L.A., Lemaitre R.N., Smith N.L., et al. Common genetic variation in six lipid-related and statin-related genes, statin use and risk of incident nonfatal myocardial infarction and stroke. Pharmacogenet Genomics 2008, 18(8):677-682.
66. Iakoubova O.A., Tong C.H., Rowland C.M., 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 2008, 51(4):435-443.
67. Maitland-van der Zee A.H., Peters B.J., Lynch A.I., et al. The effect of nine common polymorphisms in coagulation factor genes (F2, F5, F7, F12 and F13) on the effectiveness of statins: the GenHAT study. Pharmacogenet Genomics 2009, 19(5):338-344.
68. Peters B.J., Rodin A.S., Klungel O.H., et al. Variants of ADAMTS1 modify the effectiveness of statins in reducing the risk of myocardial infarction. Pharmacogenet Genomics 2010, 20(12):766-774.
69. Sabatine M.S., Ploughman L., Simonsen K.L., et al. Association between ADAMTS1 matrix metalloproteinase gene variation, coronary heart disease, and benefit of statin therapy. Arterioscler Thromb Vasc Biol 2008, 28(3):562-567.
70. Li Y., Iakoubova O., Shiffman D., et al. KIF6 polymorphism as a predictor of risk of coronary events and of clinical event reduction by statin therapy. Am J Cardiol 2010, 106(7):994-998.
71. Assimes T.L., 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 2010, 56(19):1552-1563.
72. Hopewell J.C., 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 2011, 57(20):2000-2007.
73. Ridker P.M., Macfadyen J.G., Glynn R.J., et al. Kinesin-like protein 6 (KIF6) polymorphism and the Efficacy of rosuvastatin in primary prevention. Circ Cardiovasc Genet 2011, 4(3):312-317.
74. Iakoubova O.A., Robertson M., Tong C.H., et al. KIF6 Trp719Arg polymorphism and effect of statin therapy in elderly patients: results from the PROSPER study. Eur J Cardiovasc Prev Rehabil 2010, 17(4):455-461.
75. Iakoubova O.A., Sabatine M.S., Rowland C.M., 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 2008, 51(4):449-455.
76. Bays H. Statin safety: an overview and assessment of the data-2005. Am J Cardiol 2006, 97(8A):6C-26C.
77. Fernandez G., Spatz E.S., Jablecki C., et al. Statin myopathy: a common dilemma not reflected in clinical trials. Cleve Clin J Med 2011, 78(6):393-403.
78. Available at: Accessed September 20, 2011. http://www.fda.gov/Drugs/DrugSafety/ucm256581.htm.
79. Available at: Accessed September 20, 2011. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm172268.htm.
80. National Cholesterol Education Program (NCEP) Expert Panel on Detection E, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002, 106(25):3143-3421.
81. Ghatak A., Faheem O., Thompson P.D. The genetics of statin-induced myopathy. Atherosclerosis 2010, 210(2):337-343.
82. Vladutiu G.D., Simmons Z., Isackson P.J., et al. Genetic risk factors associated with lipid-lowering drug-induced myopathies. Muscle Nerve 2006, 34(2):153-162.
83. Voora D., Shah S.H., Spasojevic I., et al. The SLCO1B1*5 genetic variant is associated with statin-induced side effects. J Am Coll Cardiol 2009, 54(17):1609-1616.
84. Brunham L.R., Lansberg P.J., Zhang L., et al. Differential effect of the rs4149056 variant in SLCO1B1 on myopathy associated with simvastatin and atorvastatin. Pharmacogenomics J 2011, [Epub ahead of print].
85. Linde R., Peng L., Desai M., et al. The role of vitamin D and SLCO1B1*5 gene polymorphism in statin-associated myalgias. Dermatoendocrinol 2010, 2(2):77-84.
86. 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. Clin Pharmacol Ther 2011, 89(2):210-216.
87. Marciante K.D., Durda J.P., Heckbert S.R., et al. Cerivastatin, genetic variants, and the risk of rhabdomyolysis. Pharmacogenet Genomics 2011, 21(5):280-288.
88. Morimoto K., Oishi T., Ueda S., et al. A novel variant allele of OATP-C (SLCO1B1) found in a Japanese patient with pravastatin-induced myopathy. Drug Metab Pharmacokinet 2004, 19(6):453-455.
89. Niemi M. Transporter pharmacogenetics and statin toxicity. Clin Pharmacol Ther 2010, 87(1):130-133.
90. Peters B.J., Klungel O.H., Visseren F.L., et al. Pharmacogenomic insights into treatment and management of statin-induced myopathy. Genome Med 2009, 1(12):120.