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.)
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The SEARCH genome-wide association study 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 3% in heterozygotes and 0.6% in those without risk alleles.
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
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 · see citing works
Haploview: analysis and visualization of LD and haplotype maps
Barrett, J., Fry, B., Maller, J., & Daly, M. (2005) · Bioinform. · doi:10.1093/bioinformatics/bth457 · Cited by 15,086 · see citing works
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 · see citing works
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 · see citing works
A haplotype map of the human genome
The International HapMap Consortium (2005) · Nature · doi:10.1038/nature04226 · Cited by 5,858 · see citing works
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 · see citing works
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 · see citing works
Thompson, P. D., Clarkson, P., & Karas, R. H. (2003) · JAMA · doi:10.1001/jama.289.13.1681 · Cited by 1,463 · see citing works
de Lemos, J. A., Blazing, M. A., Wiviott, S. D., Lewis, E. F., Fox, K. A. A., White, H. D., Rouleau, J.-L., Pedersen, T. R., Gardner, L. H., Mukherjee, R., et al. (2004) · JAMA · doi:10.1001/jama.292.11.1307 · Cited by 1,333 · see citing works
The safety of statins in clinical practice
Armitage, J. (2007) · The Lancet · doi:10.1016/s0140-6736(07)60716-8 · Cited by 833 · see citing works
Statin Safety: A Systematic Review
Law, M., & Rudnicka, A. R. (2006) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2005.12.010 · Cited by 808 · see citing works
Meta-analysis of cardiovascular outcomes trials comparing intensive versus moderate statin therapy
Cannon, C. P., Steinberg, B. A., Murphy, S. A., Mega, J. L., & Braunwald, E. (2006) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2006.04.070 · Cited by 770 · see citing works
Tirona, R. G., Leake, B. F., Merino, G., & Kim, R. B. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103792200 · Cited by 625 · see citing works
Niemi, M., Backman, J. T., Kajosaari, L. I., Leathart, J. B. S., Neuvonen, M., Daly, A. K., Eichelbaum, M. F., Kivistö, K., & Neuvonen, P. J. (2005) · Clinical Pharmacology & Therapeutics · doi:10.1016/j.clpt.2005.01.018 · Cited by 361 · see citing works
Pharmacogenomics of human OATP transporters
König, J., Seithel‐Keuth, A., Gradhand, U., & Fromm, M. F. (2006) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-006-0040-y · Cited by 358 · see citing works
Genetic risk factors associated with lipid-lowering drug-induced myopathies
Vladutiu, G. D., Simmons, Z., Isackson, P. J., Tarnopolsky, M., Peltier, W. L., Barboi, A. C., Sripathi, N., Wortmann, R. L., & Phillips, P. S. (2006) · Muscle & Nerve · doi:10.1002/mus.20567 · Cited by 253 · see citing works
Fiegenbaum, M., DASILVEIRA, F., VANDERSAND, C., VANDERSAND, L., Ferreira, M. B. C., PIRES, R., & Hutz, M. H. (2005) · Clinical Pharmacology & Therapeutics · doi:10.1016/j.clpt.2005.08.003 · Cited by 216 · see citing works
Genetic determinants of statin intolerance
Oh, J., Ban, M. R., Miskie, B. A., Pollex, R. L., & Hegele, R. A. (2007) · Lipids in Health and Disease · doi:10.1186/1476-511x-6-7 · Cited by 153 · see citing works
Mulder, A. B., van Lijf, H. J., Bon, M. A. M., Bergh, F. A. J. T. M. V. D., Touw, D. J., Neef, C., & Vermes, I. (2001) · Clinical Pharmacology & Therapeutics · doi:10.1016/s0009-9236(01)25429-0 · Cited by 136 · see citing works
Pasanen, M. K., Backman, J. T., Neuvonen, P. J., & Niemi, M. (2006) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-006-0123-1 · Cited by 119 · see citing works
Kajinami, K., Brousseau, M. E., Ordovás, J. M., & Schaefer, E. J. (2003) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2003.08.078 · Cited by 109 · see citing works
Mulder, A. B. (2001) · Clinical Pharmacology & Therapeutics · doi:10.1067/mcp.2001.120251 · Cited by 92 · see citing works
Whole-Genome Genotyping of Haplotype Tag Single Nucleotide Polymorphisms
Gunderson, K. L., Kuhn, K. M., Steemers, F. J., Ng, P. C., Murray, S. S., & Shen, R. (2006) · Pharmacogenomics · doi:10.2217/14622416.7.4.641 · Cited by 83 · see citing works
CYP2D6*4 polymorphism is associated with statin-induced muscle effects
Frudakis, T., Thomas, M. J., Ginjupalli, S., Handelin, B., Gabriel, R., & Gomez, H. (2007) · Pharmacogenetics & Genomics · doi:10.1097/fpc.0b013e328012d0a9 · Cited by 75 · see citing works
OATP-C(OATP01B1)*15 is associated with statin-induced myopathy in hypercholesterolemic patients
Morimoto, K., Ueda, S., Seki, N., IGAWA, Y., KAMEYAMA, Y., Shimizu, A., Oishi, T., Hosokawa, M., Iesato, K., & Mori, S. (2005) · Clinical Pharmacology & Therapeutics · doi:10.1016/j.clpt.2004.11.081 · Cited by 25 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Study of the effectiveness of additional reductions in cholesterol and homo- cysteine (SEARCH): characteristics of a randomized trial among 12064 myocar- dial infarction survivors. Am Heart J 2007; 154:815-23, 823.e1-823.e6. electronic
Cited by
Sorted by citations
Heart Disease and Stroke Statistics—2019 Update: A Report From the American Heart Association
Benjamin, E. J., Muntner, P., Alonso, A., Bittencourt, M. S., Callaway, C. W., Carson, A. P., Chamberlain, A. M., Chang, A. R., Cheng, S., Das, S. R., et al. (2019) · Circulation · doi:10.1161/cir.0000000000000659 · Cited by 9,036 · see citing works
Heart disease and stroke statistics-2018 update: a report from the american heart association
Benjamin, E. J., Virani, S. S., Callaway, C. W., Chamberlain, A. M., Chang, A. R., Cheng, S., Chiuve, S. E., Cushman, M., Delling, F. N., Deo, R., et al. (2018) · Circulation · doi:10.1161/cir.0000000000000558 · Cited by 7,146 · see citing works
Membrane transporters in drug development
The International Transporter Consortium, Giacomini, K. M., Huang, S.-M., Tweedie, D. J., Benet, L. Z., Brouwer, K. L. R., Chu, X., Dahlin, A., Evers, R., Fischer, V., et al. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3028 · Cited by 3,340 · see citing works
Meschia, J. F., Bushnell, C., Boden-Albala, B., Braun, L. T., Bravata, D. M., Chaturvedi, S., Creager, M. A., Eckel, R. H., Elkind, M. S. V., Fornage, M., et al. (2014) · Stroke · doi:10.1161/str.0000000000000046 · Cited by 2,650 · see citing works
Baigent, C., Landray, M. J., Reith, C., Emberson, J., Wheeler, D. C., Tomson, C., Wanner, C., Krane, V., Cass, A., Craig, J., et al. (2011) · The Lancet · doi:10.1016/s0140-6736(11)60739-3 · Cited by 2,479 · see citing works
Benefits and limitations of genome-wide association studies
Tam, V., Patel, N. K., Turcotte, M., Bossé, Y., Paré, G., & Meyre, D. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0127-1 · Cited by 2,092 · see citing works
Interpretation of the evidence for the efficacy and safety of statin therapy
Collins, R., Reith, C., Emberson, J., Armitage, J., Baigent, C., Blackwell, L., Blumenthal, R., Danesh, J., Smith, G. D., DeMets, D., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)31357-5 · Cited by 1,857 · see citing works
Genomewide Association Studies and Assessment of the Risk of Disease
Manolio, T. A. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0905980 · Cited by 1,512 · see citing works
Stroes, E. S., Thompson, P. D., Corsini, A., Vladutiu, G. D., Raal, F. J., Ray, K. K., Roden, M., Stein, E., Tokgözoğlu, L., Nordestgaard, B. G., et al. (2015) · European Heart Journal · doi:10.1093/eurheartj/ehv043 · Cited by 1,443 · see citing works
KDOQI clinical practice guideline for diabetes and CKD: 2012 update
(2012) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2012.07.005 · Cited by 1,320 · see citing works
Goldstein, L. B., Bushnell, C. D., Adams, R. J., Appel, L. J., Braun, L. T., Chaturvedi, S., Creager, M. A., Culebras, A., Eckel, R. H., Hart, R. G., et al. (2011) · Stroke · doi:10.1161/str.0b013e3181fcb238 · Cited by 1,306 · see citing works
Godoy, P., Hewitt, N. J., Albrecht, U., Andersen, M. E., Ansari, N., Bhattacharya, S., Bode, J. G., Bolleyn, J., Borner, C., Böttger, J., et al. (2013) · Archives of Toxicology · doi:10.1007/s00204-013-1078-5 · Cited by 1,280 · see citing works
Uncovering the roles of rare variants in common disease through whole-genome sequencing
Cirulli, E. T., & Goldstein, D. B. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2779 · Cited by 1,136 · see citing works
Human genetic variation and its contribution to complex traits
Frazer, K. A., Murray, S. S., Schork, N. J., & Topol, E. J. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2554 · Cited by 1,073 · see citing works
Human metabolic individuality in biomedical and pharmaceutical research
CARDIoGRAM, Suhre, K., Shin, S.-Y., Petersen, A.-K., Mohney, R. P., Meredith, D., Wägele, B., Altmaier, E., Deloukas, P., Erdmann, J., et al. (2011) · Nature · doi:10.1038/nature10354 · Cited by 1,017 · see citing works
Impact of OATP transporters on pharmacokinetics
Kalliokoski, A., & Niemi, M. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00430.x · Cited by 994 · see citing works
Xenobiotic, Bile Acid, and Cholesterol Transporters: Function and Regulation
Klaassen, C. D., & Aleksunes, L. M. (2010) · Pharmacological Reviews · doi:10.1124/pr.109.002014 · Cited by 808 · see citing works
Ward, N. C., Watts, G. F., & Eckel, R. H. (2019) · Circulation Research · doi:10.1161/circresaha.118.312782 · Cited by 772 · see citing works
Goldstein, L. B., Bushnell, C., Adams, R. J., Appel, L. J., Braun, L. T., Chaturvedi, S., Creager, M. A., Culebras, A., Eckel, R. H., Hart, R. G., et al. (2011) · Stroke · Cited by 745 · see citing works
Statin-Associated Side Effects
Thompson, P. D., Panza, G. A., Zaleski, A. L., & Taylor, B. A. (2016) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2016.02.071 · Cited by 756 · see citing works
Newman, C. B., Preiss, D., Tobert, J. A., Jacobson, T. A., Page, R. L., II, Goldstein, L. B., Chin, C. C., Tannock, L. R., Miller, M. J., Raghuveer, G., et al. (2019) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atv.0000000000000073 · Cited by 760 · see citing works
Sirtori, C. R. (2014) · Pharmacological Research · doi:10.1016/j.phrs.2014.03.002 · Cited by 705 · see citing works
Mammen, A. L., Chung, T., Christopher‐Stine, L., Rosen, P., Rosen, A., Maurer, K. D., & Casciola-Rosen, L. A. (2010) · Arthritis & Rheumatism · doi:10.1002/art.30156 · Cited by 694 · see citing works
Clinical assessment incorporating a personal genome
Ashley, E. A., Butte, A. J., Wheeler, M. T., Chen, R., Klein, T. E., Dewey, F. E., Dudley, J. T., Ormond, K. E., Pavlovic, A., Morgan, A. A., et al. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60452-7 · Cited by 674 · see citing works
HPS2-THRIVE Collaborative Group, Haynes, R., Jiang, L., Hopewell, J. C., Li, J., Chen, F., Parish, S., Landray, M. J., Collins, R., Armitage, J., et al. (2013) · European Heart Journal · doi:10.1093/eurheartj/eht055 · Cited by 676 · see citing works
Niemi, M., Pasanen, M. K., & Neuvonen, P. J. (2011) · Pharmacological Reviews · doi:10.1124/pr.110.002857 · Cited by 636 · see citing works
224th ENMC International Workshop:
Allenbach, Y., Mammen, A. L., Benvéniste, O., Stenzel, W., Allenbach, Y., Amato, A. A., Aussey, A., Benvéniste, O., Bleecker, J. D., de Groot, I., et al. (2017) · Neuromuscular Disorders · doi:10.1016/j.nmd.2017.09.016 · Cited by 586 · see citing works
Kopin, L., & Lowenstein, C. J. (2017) · Annals of Internal Medicine · doi:10.7326/aitc201712050 · Cited by 589 · see citing works
Transporters and Drug-Drug Interactions: Important Determinants of Drug Disposition and Effects
König, J., Müller, F., & Fromm, M. F. (2013) · Pharmacological Reviews · doi:10.1124/pr.113.007518 · Cited by 576 · see citing works
Statin Adverse Effects: A Review of the Literature and Evidence for a Mitochondrial Mechanism
Golomb, B. A., & Evans, M. A. (2008) · American Journal of Cardiovascular Drugs · doi:10.2165/0129784-200808060-00004 · Cited by 677 · see citing works
Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group (2010) · The Lancet · doi:10.1016/s0140-6736(10)60310-8 · Cited by 558 · see citing works
Anti-PCSK9 Antibody Effectively Lowers Cholesterol in Patients With Statin Intolerance
Stroes, E., Colquhoun, D., Sullivan, D., Civeira, F., Rosenson, R. S., Watts, G. F., Bruckert, E., Cho, L., Dent, R., Knusel, B., et al. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2014.03.019 · Cited by 526 · see citing works
What do drug transporters really do?
Nigám, S. K. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4461 · Cited by 531 · see citing works
The SLCO1B1*5Genetic Variant Is Associated With Statin-Induced Side Effects
Voora, D., Shah, S. H., Spasojević, I., Ali, S. Y., Reed, C. R., Salisbury, B. A., & Ginsburg, G. S. (2009) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2009.04.053 · Cited by 498 · see citing works
An assessment by the statin muscle safety task force: 2014 update
Rosenson, R. S., Baker, S. K., Jacobson, T. A., Kopecky, S. L., & Parker, B. A. (2014) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2014.03.004 · Cited by 485 · see citing works
Bayesian statistical methods for genetic association studies
Stephens, M., & Balding, D. J. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2615 · Cited by 465 · see citing works
Pharmacogenetics, Pharmacogenomics, and Individualized Medicine
Ma, Q., & Lu, A. Y. H. (2011) · Pharmacological Reviews · doi:10.1124/pr.110.003533 · Cited by 466 · see citing works
Narrative review: statin-related myopathy
Joy, T. R., & Hegele, R. A. (2009) · Annals of Internal Medicine · doi:10.7326/0003-4819-150-12-200906160-00009 · Cited by 453 · see citing works
Roden, D. M., McLeod, H. L., Relling, M. V., Williams, M. S., Mensah, G. A., Peterson, J. F., & Driest, S. L. V. (2019) · The Lancet · doi:10.1016/s0140-6736(19)31276-0 · Cited by 446 · see citing works
Ramsey, L. B., Johnson, S. G., Caudle, K. E., Haidar, C. E., Voora, D., Wilke, R. A., Maxwell, W. D., McLeod, H. L., Krauss, R. M., Roden, D. M., et al. (2014) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2014.125 · Cited by 434 · see citing works
ABCG2 Polymorphism Markedly Affects the Pharmacokinetics of Atorvastatin and Rosuvastatin
Keskitalo, J. E., Zolk, O., Fromm, M. F., Kurkinen, K. J., Neuvonen, P. J., & Niemi, M. (2009) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2009.79 · Cited by 417 · see citing works
Current Concepts of Mechanisms in Drug-Induced Hepatotoxicity
Russmann, S., Kullak-Ublick, G. A., & Grattagliano, I. (2009) · Current Medicinal Chemistry · doi:10.2174/092986709788803097 · Cited by 412 · see citing works
SLCO1B1 polymorphism markedly affects the pharmacokinetics of lovastatin acid
Tornio, A., Vakkilainen, J., Neuvonen, M., Backman, J. T., Neuvonen, P. J., & Niemi, M. (2015) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0000000000000148 · Cited by 410 · see citing works
Personalized Medicine: Progress and Promise
Chan, I. S., & Ginsburg, G. S. (2011) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-082410-101446 · Cited by 399 · see citing works
The SLCO (former SLC21) superfamily of transporters
Hagenbuch, B., & Stieger, B. (2013) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2012.10.009 · Cited by 384 · see citing works
van de Steeg, E., Stránecký, V., Hartmannová, H., Nosková, L., Hřebı́ček, M., Wagenaar, E., van Esch, A., de Waart, D. R., Elferink, R. P. J. O., Kenworthy, K. E., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59526 · Cited by 379 · see citing works
Pharmacogenomics of Drug Metabolizing Enzymes and Transporters: Relevance to Precision Medicine
Ahmed, S., Zhou, Z. M., Zhou, J., & Chen, S. (2016) · Genomics Proteomics & Bioinformatics · doi:10.1016/j.gpb.2016.03.008 · Cited by 395 · see citing works
Karlgren, M., Vildhede, A. M., Norinder, U., Wiśniewski, J. R., Kimoto, E., Lai, Y., Haglund, U., & Artursson, P. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm300212s · Cited by 370 · see citing works
Cooper‐DeHoff, R. M., Niemi, M., Ramsey, L. B., Luzum, J. A., Tarkiainen, E. K., Straka, R. J., Gong, L., Tuteja, S., Wilke, R. A., Wadelius, M., et al. (2022) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.2557 · Cited by 366 · see citing works
Statin-Associated Autoimmune Myopathy
Mammen, A. L. (2016) · New England Journal of Medicine · doi:10.1056/nejmra1515161 · Cited by 366 · see citing works
Emerging Role of Precision Medicine in Cardiovascular Disease
Leopold, J. A., & Loscalzo, J. (2018) · Circulation Research · doi:10.1161/circresaha.117.310782 · Cited by 373 · see citing works
Drug Transporters in Drug Efficacy and Toxicity
DeGorter, M. K., Xia, C. Q., Yang, J. J., & Kim, R. B. (2011) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010611-134529 · Cited by 359 · see citing works
Quality Control Procedures for Genome‐Wide Association Studies
Turner, S., Armstrong, L. L., Bradford, Y., Carlson, C. S., Crawford, D. C., Crenshaw, A., de Andrade, M., Doheny, K. F., Haines, J. L., Hayes, M. G., et al. (2011) · Current Protocols in Human Genetics · doi:10.1002/0471142905.hg0119s68 · Cited by 358 · see citing works
Bringing genome-wide association findings into clinical use
Manolio, T. A. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3523 · Cited by 350 · see citing works
Watanabe, T., Kusuhara, H., Maeda, K., Shitara, Y., & Sugiyama, Y. (2008) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.108.146647 · Cited by 351 · see citing works
Immune‐mediated necrotizing myopathy associated with statins
Grable-Esposito, P., Katzberg, H. D., Greenberg, S. A., Srinivasan, J., Katz, J., & Amato, A. A. (2009) · Muscle & Nerve · doi:10.1002/mus.21486 · Cited by 340 · see citing works
(2016) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(16)30156-5 · Cited by 338 · see citing works
Abraldes, J. G., Villanueva, C., Aracil, C., Turnes, J., Hernandez-Guerra, M., Genesca, J., Rodriguez, M., Castellote, J., García-Pagán, J. C., Torres, F., et al. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.01.004 · Cited by 339 · see citing works
Smith, G. D. (2011) · International Journal of Epidemiology · doi:10.1093/ije/dyr117 · Cited by 334 · see citing works
Chen, L., Zhernakova, D. V., Kurilshikov, A., Andreu-Sánchez, S., Wang, D., Augustijn, H. E., Vich Vila, A., Study, L. C., Weersma, R. K., Medema, M. H., et al. (2022) · Nature Medicine · doi:10.1038/s41591-022-02014-8 · Cited by 327 · see citing works
Wilke, R. A., Ramsey, L. B., Johnson, S. G., Maxwell, W. D., McLeod, H. L., Voora, D., Krauss, R. M., Roden, D. M., Feng, Q., Cooper‐DeHoff, R. M., et al. (2012) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2012.57 · Cited by 332 · see citing works
Transporter Pharmacogenetics and Statin Toxicity
Niemi, M. (2009) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2009.197 · Cited by 329 · see citing works
Predicting Clearance Mechanism in Drug Discovery: Extended Clearance Classification System (ECCS)
Varma, M. V., Steyn, S. J., Allerton, C., & El-Kattan, A. F. (2015) · Pharmaceutical Research · doi:10.1007/s11095-015-1749-4 · Cited by 334 · see citing works
Nielsen, S. F., & Nordestgaard, B. G. (2015) · European Heart Journal · doi:10.1093/eurheartj/ehv641 · Cited by 329 · see citing works
Rhabdomyolysis: historical background, clinical, diagnostic and therapeutic features
Cervellin, G., Comelli, I., & Lippi, G. (2010) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2010.151 · Cited by 323 · see citing works
Ross, C. J., Katzov-Eckert, H., Dubé, M., Brooks, B., Rassekh, S. R., Barhdadi, A., Zada, Y. F., Visscher, H., Brown, A. M. K., Rieder, M. J., et al. (2009) · Nature Genetics · doi:10.1038/ng.478 · Cited by 323 · see citing works
A Genome-wide Association Study of the Human Metabolome in a Community-Based Cohort
Rhee, E. P., Ho, J. E., Chen, M., Shen, D., Cheng, S. C., Larson, M. G., Ghorbani, A., Shi, X. D., Helenius, I. T., O’Donnell, C. J., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.06.013 · Cited by 318 · see citing works
Statin-induced myopathy: a review and update
Abd, T. T., & Jacobson, T. A. (2011) · Expert Opinion on Drug Safety · doi:10.1517/14740338.2011.540568 · Cited by 320 · see citing works
Okamura, T., Tsukamoto, K., Arai, H., Fujioka, Y., Ishigaki, Y., Koba, S., Ohmura, H., Shoji, T., Yokote, K., Yoshida, H., et al. (2023) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.gl2022 · Cited by 317 · see citing works
A large electronic-health-record-based genome-wide study of serum lipids
Hoffmann, T. J., Theusch, E., Haldar, T., Ranatunga, D. K., Jorgenson, E., Medina, M. W., Kvale, M. N., Kwok, P., Schaefer, C. A., Krauss, R. M., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0064-5 · Cited by 286 · see citing works
Chasman, D. I., Giulianini, F., MacFadyen, J., Barratt, B. J., Nyberg, F., & Ridker, P. M. (2012) · Circulation: Cardiovascular Genetics · doi:10.1161/circgenetics.111.961144 · Cited by 285 · see citing works
Pathogenesis of cholestatic liver disease and therapeutic approaches
Hirschfield, G. M., Heathcote, E. J., & Gershwin, M. E. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.09.004 · Cited by 287 · see citing works
Genomics of Cardiovascular Disease
O’Donnell, C. J., & Nabel, E. G. (2011) · New England Journal of Medicine · doi:10.1056/nejmra1105239 · Cited by 279 · see citing works
The neurobiology of individual differences in complex behavioral traits
Hariri, A. R. (2009) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.051508.135335 · Cited by 273 · see citing works
Red Yeast Rice for Dyslipidemia in Statin-Intolerant Patients: A Randomized Trial
Becker, D. J., Gordon, R. Y., Halbert, S. C., French, B., Morris, P. B., & Rader, D. J. (2009) · Annals of Internal Medicine · doi:10.7326/0003-4819-150-12-200906160-00006 · Cited by 275 · see citing works
Stieger, B. (2010) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-14541-4_5 · Cited by 268 · see citing works
Postmus, I., Trompet, S., Deshmukh, H., Barnes, M. R., Li, X., Warren, H. R., Chasman, D. I., Zhou, K., Arsenault, B. J., Donnelly, L. A., et al. (2014) · Nature Communications · doi:10.1038/ncomms6068 · Cited by 268 · see citing works
Topol, E. J., Bousser, M.-G., Fox, K. A., Creager, M. A., Despres, J.-P., Easton, J. D., Hamm, C. W., Montalescot, G., Steg, P. G., Pearson, T. A., et al. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60935-x · Cited by 266 · see citing works
Nies, A. T., Niemi, M., Burk, O., Winter, S., Zanger, U. M., Stieger, B., Schwab, M. G., & Schaeffeler, E. (2013) · Genome Medicine · doi:10.1186/gm405 · Cited by 268 · see citing works
Genome-wide association studies in pharmacogenomics
Daly, A. K. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2751 · Cited by 264 · see citing works
Comprehensive Pharmacogenetic Analysis of Irinotecan Neutropenia and Pharmacokinetics
Innocenti, F., Kroetz, D. L., Schuetz, E. G., Dolan, M. E., Ramı́rez, J., Relling, M. V., Chen, P., Das, S., Rosner, G. L., & Ratain, M. J. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.20.6300 · Cited by 264 · see citing works
Scott, S. A., Sangkuhl, K., Shuldiner, A. R., Hulot, J., Thorn, C. F., Altman, R. B., & Klein, T. E. (2011) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0b013e32834d4962 · Cited by 262 · see citing works
Rare versus common variants in pharmacogenetics: SLCO1B1 variation and methotrexate dispositionPreprint
Ramsey, L. B., Bruun, G. H., Yang, W., Treviño, L. R., Vattathil, S., Scheet, P. A., Cheng, C., Rosner, G. L., Giacomini, K. M., Fan, Y., et al. (2011) · Genome Research · doi:10.1101/gr.129668.111 · Cited by 260 · see citing works
Coviello, A. D., Haring, R., Wellons, M., Vaidya, D., Lehtimäki, T., Keildson, S., Lunetta, K. L., He, C., Fornage, M., Lagou, V., et al. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002805 · Cited by 250 · see citing works
Pharmacogenomics and Individualized Medicine: Translating Science Into Practice
Crews, K. R., Hicks, J. K., Pui, C.-H., Relling, M. V., & Evans, W. E. (2012) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2012.120 · Cited by 255 · see citing works
Wei, M. Y., Ito, M. K., Cohen, J. D., Brinton, E. A., & Jacobson, T. A. (2013) · Journal of clinical lipidology · doi:10.1016/j.jacl.2013.03.001 · Cited by 254 · see citing works
Mancini, G. B. J., Baker, S. K., Bergeron, J., FITCHETT, D. H., Frohlich, J. J., Genest, J. J., Gupta, M., Hegele, R. A., Ng, D. S., Pearson, G. J., et al. (2016) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2016.01.003 · Cited by 253 · see citing works
Pharmacogenomics: Precision Medicine and Drug Response
Weinshilboum, R. M., & Wang, L. (2017) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2017.09.001 · Cited by 250 · see citing works
Diagnostic evaluation of rhabdomyolysis
Nance, J., & Mammen, A. L. (2015) · Muscle & Nerve · doi:10.1002/mus.24606 · Cited by 244 · see citing works
Genome-wide association meta-analysis for total serum bilirubin levels
Johnson, A. D., Kavousi, M., Smith, A. V., Chen, M., Dehghan, A., Aspelund, T., Lin, J.-P., van Duijn, C. M., Harris, T. B., Cupples, L. A., et al. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp202 · Cited by 234 · see citing works
The Spectrum of Achalasia: Lessons From Studies of Pathophysiology and High-Resolution Manometry
Kahrilas, P. J., & Boeckxstaens, G. E. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.08.038 · Cited by 234 · see citing works
Kozyra, M., Ingelman‐Sundberg, M., & Lauschke, V. M. (2016) · Genetics in Medicine · doi:10.1038/gim.2016.33 · Cited by 230 · see citing works
Statin-Induced Myopathy Is Associated with Mitochondrial Complex III Inhibition
Schirris, T. J. J., Renkema, G. H., Ritschel, T., Voermans, N. C., Bilos, A., van Engelen, B. G. M., Brandt, U., Koopman, W. J. H., Beyrath, J., Rodenburg, R. J., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.08.002 · Cited by 227 · see citing works
A statin-dependent QTL for GATM expression is associated with statin-induced myopathy
Mangravite, L. M., Engelhardt, B. E., Medina, M. W., Smith, J. D., Brown, C. D., Chasman, D. I., Mecham, B. H., Howie, B., Shim, H., Naidoo, D., et al. (2013) · Nature · doi:10.1038/nature12508 · Cited by 224 · see citing works
In vitro-in vivo Extrapolation of Transporter-mediated Clearance in the Liver and Kidney
Kusuhara, H., & Sugiyama, Y. (2009) · Drug Metabolism and Pharmacokinetics · doi:10.2133/dmpk.24.37 · Cited by 221 · see citing works
Human skeletal muscle drug transporters determine local exposure and toxicity of statins
Knauer, M. J., Urquhart, B. L., Meyer zu Schwabedissen, H. E., Schwarz, U. I., Lemke, C. J., Leake, B. F., Kim, R. B., & Tirona, R. G. (2010) · Circulation Research · doi:10.1161/circresaha.109.203596 · Cited by 222 · see citing works
Roden, D. M., Wilke, R. A., Kroemer, H. K., & Stein, C. M. (2011) · Circulation · doi:10.1161/circulationaha.109.914820 · Cited by 222 · see citing works
Liu, X. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-7647-4_3 · Cited by 224 · see citing works
Phenotype standardization for statin-induced myotoxicity
Alfirevic, A., Neely, D., Armitage, J., Chinoy, H., Cooper, R. G., Laaksonen, R., Carr, D. F., Bloch, K. M., Fahy, J., Hanson, A., et al. (2014) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2014.121 · Cited by 220 · see citing works
Mutations in LPIN1 Cause Recurrent Acute Myoglobinuria in Childhood
Zeharia, A., Shaag, A., Houtkooper, R. H., Hindi, T., de Lonlay, P., Erez, G., Hubert, L., Saada, A., de Keyzer, Y., Eshel, G. M., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.09.002 · Cited by 219 · see citing works
- 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 › Surgery › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
