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SLCO1B1 Variants and Statin-Induced Myopathy — A Genomewide Study
Open accessAbstract
BACKGROUND: Lowering low-density lipoprotein cholesterol with statin therapy results in substantial reductions in cardiovascular events, and larger reductions in cholesterol may produce larger benefits. In rare cases, myopathy occurs in association with statin therapy, especially when the statins are administered at higher doses and with certain other medications. METHODS: We carried out a genomewide association study using approximately 300,000 markers (and additional fine-mapping) in 85 subjects with definite or incipient myopathy and 90 controls, all of whom were taking 80 mg of simvastatin daily as part of a trial involving 12,000 participants. Replication was tested in a trial of 40 mg of simvastatin daily involving 20,000 participants. RESULTS: The genomewide scan yielded a single strong association of myopathy with the rs4363657 single-nucleotide polymorphism (SNP) located within SLCO1B1 on chromosome 12 (P=4x10(-9)). SLCO1B1 encodes the organic anion-transporting polypeptide OATP1B1, which has been shown to regulate the hepatic uptake of statins. The noncoding rs4363657 SNP was in nearly complete linkage disequilibrium with the nonsynonymous rs4149056 SNP (r(2)=0.97), which has been linked to statin metabolism. The prevalence of the rs4149056 C allele in the population was 15%. The odds ratio for myopathy was 4.5 (95% confidence interval [CI], 2.6 to 7.7) per copy of the C allele, and 16.9 (95% CI, 4.7 to 61.1) in CC as compared with TT homozygotes. More than 60% of these myopathy cases could be attributed to the C variant. The association of rs4149056 with myopathy was replicated in the trial of 40 mg of simvastatin daily, which also showed an association between rs4149056 and the cholesterol-lowering effects of simvastatin. No SNPs in any other region were clearly associated with myopathy. CONCLUSIONS: We have identified common variants in SLCO1B1 that are strongly associated with an increased risk of statin-induced myopathy. Genotyping these variants may help to achieve the benefits of statin therapy more safely and effectively. (Current Controlled Trials number, ISRCTN74348595.)
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“The SEARCH genome-wide association study of SLCO1B1 variants identified a defective rs4149056 SNP in strong linkage disequilibrium with the c.521T_C SNP, which, in homozygotes, was associated with an 18% risk of muscle symptoms with high-dose simvastatin compared with heterozygotes (3%); in those without risk alleles, the risk of muscle symptoms was 0.6%.111”
From Statin-associated muscle symptoms: impact on statin therapy—European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management (2015) · cites this paper as [111]
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Cites
PLINK: a tool set for whole-genome association and population-based linkage analyses.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., Maller, J., Sklar, P., de Bakker, P. I. W., Daly, M. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/519795 · Cited by 34,089
Haploview: analysis and visualization of LD and haplotype maps
Barrett, J. C., Fry, B., Maller, J., & Daly, M. J. (2004) · Bioinformatics · doi:10.1093/bioinformatics/bth457 · Cited by 14,551
Principal components analysis corrects for stratification in genome-wide association studies
Price, A. L., Patterson, N. J., Plenge, R. M., Weinblatt, M. E., Shadick, N. A., & Reich, D. (2006) · Nature Genetics · doi:10.1038/ng1847 · Cited by 10,248
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
The Wellcome Trust Case Control Consortium, Management Committee, Burton, P. R., Clayton, D. G., Cardon, L. R., Craddock, N., Deloukas, P., Duncanson, A., Kwiatkowski, D. P., McCarthy, M. I., et al. (2007) · Nature · doi:10.1038/nature05911 · Cited by 9,442
A haplotype map of the human genome
The International HapMap Consortium (2005) · Nature · doi:10.1038/nature04226 · Cited by 5,858
Intensive versus Moderate Lipid Lowering with Statins after Acute Coronary Syndromes
Cannon, C. P., Braunwald, E., McCabe, C. H., Rader, D. J., Rouleau, J. L., Belder, R., Joyal, S. V., Hill, K. A., Pfeffer, M. A., & Skene, A. M. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040583 · Cited by 4,938
Intensive Lipid Lowering with Atorvastatin in Patients with Stable Coronary Disease
LaRosa, J. C., Grundy, S. M., Waters, D. D., Shear, C., Barter, P., Fruchart, J.-C., Gotto, A. M., Greten, H., Kastelein, J. J. P., Shepherd, J., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa050461 · Cited by 3,489
Pedersen, T. R. (2005) · JAMA · doi:10.1001/jama.294.19.2437 · Cited by 1,548
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Items 201–300 of 1,002
Genetics and Genomics for the Prevention and Treatment of Cardiovascular Disease: Update
Ganesh, S. K., Arnett, D. K., Assimes, T. L., Basson, C. T., Chakravarti, A., Ellinor, P. T., Engler, M. B., Goldmuntz, E., Herrington, D. M., Hershberger, R. E., et al. (2013) · Circulation · doi:10.1161/01.cir.0000437913.98912.1d · Cited by 130
Duke, J. D., Han, X., Wang, Z. P., Subhadarshini, A., Karnik, S., Li, X., Hall, S. D., Jin, Y., Callaghan, J. T., Overhage, J. M., et al. (2012) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002614 · Cited by 128
“In a recent GWAS study, expression of the OATP1B1 transporter was shown to predict myopathy risk associated with simvastatin [20].”
BackgroundDrug interactions evaluation: An integrated part of risk assessment of therapeutics
Zhang, L., Reynolds, K. S., Zhao, P., & Huang, S.-M. (2010) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2009.12.016 · Cited by 125
“, simvastatin, rosuvastatin, atovastatin) and may play a role in their drug interactions and their adverse drug reactions (Kiser et al., 2008; Voora et al., 2009; Kalliokoski and Niemi, 2009; Link et al., 2008).”
BackgroundPrecision Medicine Is Not Just Genomics: The Right Dose for Every Patient
Peck, R. (2017) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010617-052446 · Cited by 125
Hoffman, K. B., Kraus, C. N., Dimbil, M., & Golomb, B. A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0042866 · Cited by 127
Racial Differences in the Cholesterol-Lowering Effect of Statin
Naito, R., Miyauchi, K., & Daida, H. (2016) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.rv16004 · Cited by 123
Drug Uptake Systems in Liver and Kidney: A Historic Perspective
Hagenbuch, B. (2009) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2009.235 · Cited by 123
“Several polymorphisms have been described (35) and a genome-wide association study linked SLCO1B1 polymorphisms to an increased risk of statininduced myopathy (37) supporting the important role of OATP1B1 in the hepatic uptake of statins and possibly of additional drugs.”
BackgroundAlam, K., Crowe, A., Wang, X., Zhang, P., Ding, K., Li, L., & Yue, W. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19030855 · Cited by 123
“521T>C polymorphism is associated with increased risk of simvastatin-induced myopathy [40].”
BackgroundUsing Electronic Health Records To Generate Phenotypes For Research
Pendergrass, S. A., & Crawford, D. C. (2019) · Current Protocols in Human Genetics · doi:10.1002/cphg.80 · Cited by 120
The genetics of statin-induced myopathy
Ghatak, A., Faheem, O., & Thompson, P. D. (2009) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2009.11.033 · Cited by 118
Epidemiology of the idiopathic inflammatory myopathies
Khoo, T., Lilleker, J. B., Thong, B. Y., Leclair, V., Lamb, J. A., & Chinoy, H. (2023) · Nature Reviews Rheumatology · doi:10.1038/s41584-023-01033-0 · Cited by 138
“…is linked to non-synonymous SNP rs4149056, which had a strong and unique dosage-dependent association (OR 4.5 for each copy of the rs4149056 C allele) with statin-associated myopathy in a genome-wide association study of simvastatin users comparing 85 individuals with myopathy and 90 without 155 .”
BackgroundInfluentialStatin‐induced muscle damage and atrogin‐1 induction is the result of a geranylgeranylation defect
Cao, P., Hanai, J., Tanksale, P., Imamura, S., Sukhatme, V. P., & Lecker, S. H. (2009) · The FASEB Journal · doi:10.1096/fj.08-128843 · Cited by 117
“It is conceivable that polymorphisms in the atrogin-1 gene or promoter might explain differences in susceptibility, clinical presentation, or course in patients with statin myopathy (64).”
BackgroundStatin‐Associated Muscle‐Related Adverse Effects: A Case Series of 354 Patients
Cham, S., Evans, M. A., Denenberg, J. O., & Golomb, B. A. (2010) · Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy · doi:10.1592/phco.30.6.541 · Cited by 114
Gamazon, E. R., Huang, R. S., Cox, N. J., & Dolan, M. E. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1001827107 · Cited by 116
Importance of Hepatic Transporters in Clinical Disposition of Drugs and Their Metabolites
Patel, M., Taskar, K. S., & Zamek‐Gliszczynski, M. J. (2016) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.671 · Cited by 115
Weighing the benefits of high-dose simvastatin against the risk of myopathy
Egan, A., & Colman, E. (2011) · New England Journal of Medicine · doi:10.1056/nejmp1106689 · Cited by 113
Seitz, T., Stalmann, R., Dalila, N., Chen, J., Pojar, S., Pereira, J. N. S., Krätzner, R., Brockmöller, J., & Tzvetkov, M. V. (2015) · Genome Medicine · doi:10.1186/s13073-015-0172-0 · Cited by 113
Drug-related Myopathies of Which the Clinician Should Be Aware
Valiyil, R., & Christopher‐Stine, L. (2010) · Current Rheumatology Reports · doi:10.1007/s11926-010-0104-3 · Cited by 116
Nakanishi, T., & Tamai, I. (2011) · Drug Metabolism and Pharmacokinetics · doi:10.2133/dmpk.dmpk-11-rv-099 · Cited by 112
Bek, S., Nielsen, J. V., Bojesen, A. B., Franke, A., Bank, S., Vogel, U. B., & Andersen, V. C. (2016) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.13736 · Cited by 111
Membrane Transporters in Drug Development
Keogh, J. P. (2012) · Advances in pharmacology · doi:10.1016/b978-0-12-398339-8.00001-x · Cited by 114
Ahmad, Z. (2014) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2014.02.033 · Cited by 110
Mechanisms and assessment of statin‐related muscular adverse effects
Moßhammer, D., Schaeffeler, E., Schwab, M. G., & Mörike, K. (2014) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12360 · Cited by 112
KONES, R. J. (2010) · Drug Design Development and Therapy · doi:10.2147/dddt.s10812 · Cited by 112
“Genetic polymorphism within SLCO1B1, the gene that encodes OATP1B1, produces a variant which increases susceptibility to statin-induced myopathy.(379) Since statins affect many different molecules and signaling systems, the mechanism of statin myopathy also remains uncertain.”
BackgroundRiedmaier, S., Klein, K., Hofmann, U., Keskitalo, J. E., Neuvonen, P. J., Schwab, M. G., Niemi, M., & Zanger, U. M. (2009) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2009.181 · Cited by 113
Warden, B. A., Guyton, J. R., Kovacs, A. C., Durham, J. A., Jones, L. K., Dixon, D. L., Jacobson, T. A., & Duell, P. B. (2023) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2022.09.001 · Cited by 111
“18 Patients often experience marked improvement in symptoms within 2-4 weeks following statin discontinuation.”
Statin myotoxicity: a review of genetic susceptibility factors
Needham, M., & Mastaglia, F. L. (2014) · Neuromuscular Disorders · doi:10.1016/j.nmd.2013.09.011 · Cited by 108
“63% risk in the group that were homozygous for the low-risk allele [97].”
InfluentialBenefit of Preemptive Pharmacogenetic Information on Clinical Outcome
Roden, D. M., Driest, S. L. V., Mosley, J. D., Wells, Q. S., Robinson, J. R., Denny, J. C., & Peterson, J. F. (2018) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.1035 · Cited by 110
“In the case of simvastatin, a specific variant in SLCO1B1 has been associated with a dramatically increased risk of biochemically proven myopathy among patients receiving high-dose (80mg per day) simvastatin.(36) In both of these settings, therefore, preemptive genotyping could be useful (as suggested in the current C…”
BackgroundFahrmayr, C., Fromm, M. F., & König, J. (2010) · Drug Metabolism Reviews · doi:10.3109/03602530903491683 · Cited by 108
“Further, in a genomewide-association study using approximately 300,000 markers in 85 patients with definite or incipient myopathy (and 90 controls), this variation was identified to be strongly associated with the risk of simvastatin-induced myopathy (Link et al., 2008).”
BackgroundWatanabe, T., Kusuhara, H., & Sugiyama, Y. (2010) · Journal of Pharmacokinetics and Pharmacodynamics · doi:10.1007/s10928-010-9176-y · Cited by 110
“It is reasonable that the frequency of the OATP1B1*15 haplotype was significantly higher in patients who experienced myopathy after receiving pravastatin or atorvastatin than in patients without myopathy [52], and that the variants in OATP1B1 are strongly associated with an increased risk of simvastatin-induced myopat…”
BackgroundThe Roles of Coenzyme Q in Disease: Direct and Indirect Involvement in Cellular Functions
Pallotti, F., Bergamini, C., Lamperti, C., & Fato, R. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms23010128 · Cited by 109
“A common variation in this gene was found to significantly increase the risk of myopathy [75].”
BackgroundThe physiological role of drug transporters
Liang, Y., Li, S., & Chen, L. (2015) · Protein & Cell · doi:10.1007/s13238-015-0148-2 · Cited by 118
Using Genome-Wide Association Studies to Identify Genes Important in Serious Adverse Drug Reactions
Daly, A. K. (2011) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010611-134743 · Cited by 105
Strategic Approaches to Unraveling Genetic Causes of Cardiovascular Diseases
Marian, A. J., & Belmont, J. W. (2011) · Circulation Research · doi:10.1161/circresaha.110.236067 · Cited by 109
Implementation and utilization of genetic testing in personalized medicine
Scott, S., Abul-Husn, N., Owusu Obeng, A., Sanderson, S., & Gottesman, O. (2014) · Pharmacogenomics and Personalized Medicine · doi:10.2147/pgpm.s48887 · Cited by 106
Bailey, K. M., Romaine, S. P. R., Jackson, B. M., Farrin, A. J., Efthymiou, M., Barth, J. H., Copeland, J., McCormack, T., Whitehead, A. L., Flather, M. D., et al. (2010) · Circulation Cardiovascular Genetics · doi:10.1161/circgenetics.109.898502 · Cited by 106
Pharmacogenomics in clinical practice and drug development
Harper, A. R., & Topol, E. J. (2012) · Nature Biotechnology · doi:10.1038/nbt.2424 · Cited by 109
Cerivastatin, genetic variants, and the risk of rhabdomyolysis
Marciante, K. D., Durda, J. P., Heckbert, S. R., Lumley, T., Rice, K. M., McKnight, B., Totah, R. A., Tamraz, B., Kroetz, D. L., Fukushima, H., et al. (2011) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0b013e328343dd7d · Cited by 106
Hopewell, J. C., Parish, S., Offer, A. R., Link, E. K., Clarke, R., Lathrop, M. G., Armitage, J., Collins, R., & on behalf of the MRC/BHF Heart Protection Study Collaborative Group (2012) · European Heart Journal · doi:10.1093/eurheartj/ehs344 · Cited by 107
Adverse drug reactions and organ damage: The liver
Licata, A. (2016) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2015.12.017 · Cited by 109
Pharmacogenetics: past, present and future
Pirmohamed, M. (2011) · Drug Discovery Today · doi:10.1016/j.drudis.2011.08.006 · Cited by 105
Electronic health record design and implementation for pharmacogenomics: a local perspective
Peterson, J. F., Bowton, E., Field, J. R., Beller, M., Mitchell, J. M., Schildcrout, J. S., Gregg, W. M., Johnson, K. B., Jirjis, J. N., Roden, D. M., et al. (2013) · Genetics in Medicine · doi:10.1038/gim.2013.109 · Cited by 105
Stenzel, W., Goebel, H. H., & Aronica, E. (2012) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2012.01302.x · Cited by 106
Nuclear Receptors in Drug Metabolism, Drug Response and Drug Interactions
Prakash, C., Zuniga, B., Song, C. S., Jiang, S., Cropper, J. D., Park, S.-G., & Chatterjee, B. (2015) · Nuclear Receptor Research · doi:10.11131/2015/101178 · Cited by 105
Dermatomyositis, polymyositis and immune-mediated necrotising myopathies
Luo, Y., & Mastaglia, F. L. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.05.034 · Cited by 104
Pharmacogenomics of adverse drug reactions
Daly, A. K. (2013) · Genome Medicine · doi:10.1186/gm409 · Cited by 106
“A GWA study involving 85 cases of simvastatin-induced myopathy found a significant signal for a single SNP in the gene SLCO1B1, which encodes a transporter expressed at high levels in hepatocytes [48].”
BackgroundAmato, A. (2006) · Journal watch · doi:10.1056/jn200606220000001 · Cited by 104
Pharmacogenetics and human genetic polymorphisms
Daly, A. K. (2010) · Biochemical Journal · doi:10.1042/bj20100522 · Cited by 105
Holmes, M. V., Shah, T., Vickery, C., Smeeth, L. L., Hingorani, A. D., & Casas, J. P. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007960 · Cited by 103
“SLCO1B1 variants and statin-induced myopathy, based on the SEARCH trial involving 12,064 participants) [40]”
BackgroundHu, M., Cheung, B. M. Y., & Tomlinson, B. (2012) · Therapeutic Advances in Drug Safety · doi:10.1177/2042098612439884 · Cited by 107
“A genomewide association study from the SEARCH participants taking the 80 mg dose of simvastatin and replicated in the Heart Protection Study with the 40 mg dose identified that the 521T>C in SLCO1B1 was significantly associated with simvastatin-induced myopathy [Link et al. 2008].”
BackgroundInfluentialPharmacogenetics of Drug Transporters
Franke, R. M., Gardner, E. R., & Sparreboom, A. (2009) · Current Pharmaceutical Design · doi:10.2174/138161210790112683 · Cited by 103
“increase the risk of systemic toxicity, especially statin-induced myopathy [108, 113].”
BackgroundPharmacogenomic biomarkers: new tools in current and future drug therapy
Sim, S. C., & Ingelman‐Sundberg, M. (2010) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2010.11.008 · Cited by 106
Becquemont, L., Alfirevic, A., Amstutz, U., Brauch, H. B., Jacqz-Aigrain, É., Laurent‐Puig, P., Molina‐Vila, M. Á., Niemi, M., Schwab, M. G., Somogyi, A. A., et al. (2010) · Pharmacogenomics · doi:10.2217/pgs.10.147 · Cited by 105
Danik, J. S., Chasman, D. I., MacFadyen, J. G., Nyberg, F., Barratt, B. J., & Ridker, P. M. (2013) · American Heart Journal · doi:10.1016/j.ahj.2013.01.025 · Cited by 99
Ménochet, K., Kenworthy, K. E., Houston, J. B., & Galetin, A. (2011) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.111.187112 · Cited by 98
Izumi, S., Nozaki, Y., Komori, T., Maeda, K., Takenaka, O., Kusano, K., Yoshimura, T., Kusuhara, H., & Sugiyama, Y. (2013) · Drug Metabolism and Disposition · doi:10.1124/dmd.113.052290 · Cited by 99
“, 2011) and adverse event rates of statin therapy (Link et al., 2008).”
BackgroundPrediction of Pharmacokinetics and Drug–Drug Interactions When Hepatic Transporters are Involved
Li, R., Barton, H. A., & Varma, M. V. S. (2014) · Clinical Pharmacokinetics · doi:10.1007/s40262-014-0156-z · Cited by 98
“HMG-CoA reductase inhibitors (statins) represent an important therapeutic class for which OATPs play a key role in determining their pharmacokinetics and the target-site exposure that influences pharmacodynamic activity [9, 21–23].”
BackgroundManaging the underestimated risk of statin-associated myopathy
Rallidis, L. S., Fountoulaki, K., & ANASTASIOU‐NANA, M. I. (2011) · International Journal of Cardiology · doi:10.1016/j.ijcard.2011.07.048 · Cited by 99
Transporter-Mediated Drug Uptake and Efflux: Important Determinants of Adverse Drug Reactions
Zolk, O., & Fromm, M. F. (2011) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2010.354 · Cited by 97
Identification of Genetic Variants Associated With Response to Statin Therapy
Mega, J. L., Morrow, D. A., Brown, A. H., Cannon, C. P., & Sabatine, M. S. (2009) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.109.188474 · Cited by 100
Pharmacogenomics of Adverse Drug Reactions: Practical Applications and Perspectives
Becquemont, L. (2009) · Pharmacogenomics · doi:10.2217/pgs.09.37 · Cited by 96
Pharmacogenetics of Anti-Diabetes Drugs
DiStefano, J. K., & Watanabe, R. M. (2010) · Pharmaceuticals · doi:10.3390/ph3082610 · Cited by 96
“Variation in SLCO1B1 has been shown to be associated with slow response to pravastain [204] and with statin-induced myopathy [205].”
BackgroundGender differences in clinical registration trials: is there a real problem?
Labots, G., Jones, A. E., de Visser, S. J., Rißmann, R., & Burggraaf, J. (2018) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.13497 · Cited by 95
Precision Medicine: A New Paradigm in Therapeutics
Akhoon, N. (2021) · International Journal of Preventive Medicine · doi:10.4103/ijpvm.ijpvm_375_19 · Cited by 116
Genetic determination of the hypothalamic–pituitary–thyroid axis: where do we stand?
Medici, M., Visser, W. E., Visser, T. J., & Peeters, R. P. (2015) · Endocrine Reviews · doi:10.1210/er.2014-1081 · Cited by 92
Knop, J., Misaka, S., Singer, K., Hoier, E., Müller, F., Glaeser, H., König, J., & Fromm, M. F. (2015) · PLoS ONE · doi:10.1371/journal.pone.0139370 · Cited by 94
“SLCO1B1 polymorphisms and simvastatin-induced myopathies) [11] and concomitantly administered drugs [e.”
BackgroundLegge, S. E., Hamshere, M. L., Ripke, S., Pardiñas, A. F., Goldstein, J. I., Rees, E., Richards, A. L., Leonenko, G., Jorskog, L. F., Chambert, K. D., et al. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.97 · Cited by 94
Pharmacogenomics‐Based Point‐of‐Care Clinical Decision Support Significantly Alters Drug Prescribing
O'Donnell, P., Wadhwa, N. R., Danahey, K., Borden, B., Lee, S., Hall, J. P., Klammer, C., Hussain, S., Siegler, M. A., Sorrentino, M. J., et al. (2017) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.709 · Cited by 93
Köck, K., Koenen, A., Giese, B., Fraunholz, M. J., May, K. E., Siegmund, W., Hammer, E., Völker, U., Jedlitschky, G., Kroemer, H. K., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.056457 · Cited by 94
The AKT/mTOR signaling pathway plays a key role in statin-induced myotoxicity
Bonifacio, A., Sanvee, G. M., Bouitbir, J., & Krähenbühl, S. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2015.04.010 · Cited by 93
“While a high exposure to statins is a clearly established risk factor for statin-associatedmyopathy [1,2,7], the molecular mechanisms leading to muscle damage, in particular rhabdomyolysis, in patients treated with statins are less clear [3].”
BackgroundBouitbir, J., Singh, F., Charles, A., Schlagowski, A.-I., Bonifacio, A., Echaniz‐Laguna, A., Gény, B., Krähenbühl, S., & Zoll, J. (2015) · Antioxidants and Redox Signaling · doi:10.1089/ars.2014.6190 · Cited by 100
“…atorvastatin concentrations used in our cell experiments were higher than the concentrations normally reached in vivo [which are below 5 l M (19)], our data are in agreement with the clinical findings in humans, showing that exposure is a strong risk factor for statin-associated myopathy (22, 34).”
Badée, J., Achour, B., Rostami‐Hodjegan, A., & Galetin, A. (2015) · Drug Metabolism and Disposition · doi:10.1124/dmd.114.062034 · Cited by 91
“In most of the studies, the extent of variability in protein expression exceeds the differences associated with the well-recognized genetic variations in the SLCO1B1 and SCLO1B3 genes encoding OATP1B1 and OATP1B3, respectively (Link et al., 2008; Niemi et al., 2011; Gong and Kim, 2013).”
BackgroundParsing interindividual drug variability: an emerging role for systems pharmacology
Turner, R. M., Park, B. K., & Pirmohamed, M. (2015) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1302 · Cited by 95
Organic Anion Transporting Polypeptides: Emerging Roles in Cancer Pharmacology
Schulte, R. R., & Ho, R. H. (2019) · Molecular Pharmacology · doi:10.1124/mol.118.114314 · Cited by 97
“…is different in malignant cells (cytoplasmic) versus normal tissue (membranous) (Libra et al., 2006), and progressive loss of OATP1B3 staining is seen as tumor grade increases, suggesting that the lowest OATP1B3 expression is associated with the most aggressive tumors (Lockhart et al., 2008).”
BackgroundLee, H. H., & Ho, R. H. (2016) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.13207 · Cited by 91
Muscular effects of statins in the elderly female: a review
Schneider, E. B., Bhardwaj, & Selvarajah, S. (2013) · Clinical Interventions in Aging · doi:10.2147/cia.s29686 · Cited by 90
“55,57 However, recent studies have shown that this polymorphism might be significantly associated only with simvastatin-induced myopathy.”
InfluentialSystems-based approaches to cardiovascular disease
MacLellan, W. R., Wang, Y., & Lusis, A. J. (2012) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2011.208 · Cited by 92
Kirchhof, P. F., Medicine, E. C. R. A. E. A. W. S. O. P., Sipido, K. R., Medicine, E. C. R. A. E. A. W. S. O. P., Cowie, M., Medicine, E. C. R. A. E. A. W. S. O. P., Eschenhagen, T., Medicine, E. C. R. A. E. A. W. S. O. P., Fox, K. A. A., Medicine, E. C. R. A. E. A. W. S. O. P., et al. (2014) · European Heart Journal · doi:10.1093/eurheartj/ehu312 · Cited by 93
“the use of genetic markers to identify patients at risk for adverse reactions to pharmacotherapy, has been proposed for several cardiovascular therapeutics including antithrombotic agents, antiarrhythmic drugs,(2,57) or rhabdomyolysis on statin therapy.(58) Even though the evidence for genetically con-”
BackgroundPharmacogenomics of statins: understanding susceptibility to adverse effects
Kitzmiller, J., Mikulik, E., Dauki, A. M., Mukherjee, C., & Luzum, J. A. (2016) · Pharmacogenomics and Personalized Medicine · doi:10.2147/pgpm.s86013 · Cited by 92
Biomarkers for In Vivo Assessment of Transporter Function
Müller, F., Sharma, A., König, J., & Fromm, M. F. (2018) · Pharmacological Reviews · doi:10.1124/pr.116.013326 · Cited by 91
“Furthermore, this variant is strongly associated with an increased risk of statin-induced myopathy (Link et al., 2008).”
BackgroundSchwarz, U. I., zu Schwabedissen, H. E. M., Tirona, R. G., Suzuki, A., Leake, B. F., Mokrab, Y., Mizuguchi, K., Ho, R. H., & Kim, R. B. (2011) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0b013e328342f5b1 · Cited by 90
Phenotypic and pharmacogenetic evaluation of patients with thiazide-induced hyponatremia
Ware, J. S., Wain, L. V., Channavajjhala, S. K., Jackson, V. E., Edwards, E., Lu, R., Siew, K., Jia, W., Shrine, N. R. G., Kinnear, S., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci89812 · Cited by 90
Unmet Needs in LDL-C Lowering: When Statins Won’t Do!
Krähenbühl, S., Pavik-Mezzour, I., & von Eckardstein, A. (2016) · Drugs · doi:10.1007/s40265-016-0613-0 · Cited by 89
“SEARCH Collaborative Group [53] (randomized trial of 12,064 pts who received simvastatin 20 or 80 mg daily) Rhabdomyolysis 49 cases of ‘definite myopathy’ in the simvastatin 80-mg group vs.”
MethodInfluentialEffect of Coenzyme Q10 supplementation on statin-induced myalgias
Bookstaver, D. A., Burkhalter, N. A., & Hatzigeorgiou, C. (2012) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2012.04.026 · Cited by 89
NLA Task Force on Statin Safety - 2014 update
Jacobson, T. A. (2014) · Journal of clinical lipidology · doi:10.1016/j.jacl.2014.03.003 · Cited by 91
Fitipaldi, H., & Franks, P. W. (2022) · Human Molecular Genetics · doi:10.1093/hmg/ddac245 · Cited by 89
Tomita, Y., Maeda, K., & Sugiyama, Y. (2012) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2012.221 · Cited by 88
The Importance of Patient-Specific Factors for Hepatic Drug Response and Toxicity
Lauschke, V. M., & Ingelman‐Sundberg, M. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17101714 · Cited by 92
Rifampicin alters atorvastatin plasma concentration on the basis of SLCO1B1 521T>C polymorphism
He, Y., Zhang, W., Chen, Y., Guo, D., Tu, J., Xu, L., Tan, Z., Chen, B., Li, Z., Zhou, G., et al. (2009) · Clinica Chimica Acta · doi:10.1016/j.cca.2009.04.003 · Cited by 88
Statin drug interactions and related adverse reactions
Bellosta, S., & Corsini, A. (2012) · Expert Opinion on Drug Safety · doi:10.1517/14740338.2012.712959 · Cited by 111
Clinical Pharmacology and Pharmacogenetics in a Genomics Era: The DMET Platform
Sissung, T. M., English, B. C., Venzon, D. J., Figg, W. D., & Deeken, J. F. (2009) · Pharmacogenomics · doi:10.2217/pgs.09.154 · Cited by 87
Genetics of neuromuscular disorders
Laing, N. G. (2012) · Critical Reviews in Clinical Laboratory Sciences · doi:10.3109/10408363.2012.658906 · Cited by 88
Pharmacogenomics of adverse drug reactions: implementing personalized medicine
Wei, C.-Y., Lee, M. T. M., & Chen, Y. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds341 · Cited by 87
“Homozygous CC of the SNP rs4363657 accounts for an 18% cumulative risk of myopathy (34).”
BackgroundA preliminary study of atorvastatin plasma concentrations in critically ill patients with sepsis
Krüger, P., Freir, N. M., Venkatesh, B., Robertson, T. A., Roberts, M. S., & Jones, M. (2008) · Intensive Care Medicine · doi:10.1007/s00134-008-1358-3 · Cited by 87
Genetic susceptibility to ischemic stroke
Meschia, J. F., Worrall, B. B., & Rich, S. S. (2011) · Nature Reviews Neurology · doi:10.1038/nrneurol.2011.80 · Cited by 87
Genetic variants associated with angiotensin-converting enzyme inhibitor-associated angioedema
Paré, G., Kubo, M., Byrd, J. B., McCarty, C. A., Woodard‐Grice, A. V., Teo, K. K., Anand, S. S., Zuvich, R. L., Bradford, Y., Ross, S. A., et al. (2013) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0b013e328363c137 · Cited by 84
Personalized Sequencing and the Future of Medicine: Discovery, Diagnosis and Defeat of Disease
Esplin, E. D., Oei, L., & Snyder, M. P. (2014) · Pharmacogenomics · doi:10.2217/pgs.14.117 · Cited by 91
Statins and risk of type 2 diabetes: mechanism and clinical implications
Laakso, M., & Fernandes Silva, L. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1239335 · Cited by 82
“SLCO1B1 rs4363657 variant is strongly associated with an increased risk of statin-induced myopathy (47).”
BackgroundMital, S. R., Musunuru, K., Garg, V., Russell, M. W. W., Lanfear, D. E., Gupta, R. M., Hickey, K. T., Ackerman, M. J., Perez, M. V., Roden, D. M., et al. (2016) · Circulation Cardiovascular Genetics · doi:10.1161/hcg.0000000000000031 · Cited by 86
DNA variations in human and medical genetics: 25 years of my experience
Nakamura, Y. (2009) · Journal of Human Genetics · doi:10.1038/jhg.2008.6 · Cited by 86
Metadata
- Authors
- The SEARCH Collaborative Group
- Affiliations
- University of Oxford (GB)
- Corresponding author
- The SEARCH Collaborative Group
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2008-08-21
- Volume
- 359
- Issue
- 8
- Pages
- 789-799
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W1604547439
- Cited by
- 2,043
- References
- 27
- Citations by year
- 2026: 54 · 2025: 63 · 2024: 56 · 2023: 67 · 2022: 89 · 2021: 74 · 2020: 93 · 2019: 97 · 2018: 97 · 2017: 91 · 2016: 125 · 2015: 123 · 2014: 151 · 2013: 178 · 2012: 181
- FWCI
- 152.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- British Heart Foundation
- Medical Research Council (MC_EX_G0801669)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- statin-induced myopathy, SLCO1B1, OATP1B1, simvastatin, rs4149056, single nucleotide polymorphisms, statin metabolism, hepatic uptake, LDL cholesterol lowering, genetic susceptibility, drug-induced myopathy, linkage disequilibrium, replication study, statin dose
- MeSH terms
- Aged, Arterial Occlusive Diseases, Chromosomes, Human, Pair 12, Diabetes Mellitus, Female, Genetic Markers, Genotype, Humans, Male, Middle Aged, Muscular Diseases, Myocardial Infarction, Risk, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Simvastatin, Polymorphism, Single Nucleotide, Organic Anion Transporters, Liver-Specific Organic Anion Transporter 1
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