The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
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.)
Overview
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
Verification
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?
In the citing paper
“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.
Citations
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
Thompson, P. D., Clarkson, P., & Karas, R. H. (2003) · JAMA · doi:10.1001/jama.289.13.1681 · Cited by 1,463
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
The safety of statins in clinical practice
Armitage, J. (2007) · The Lancet · doi:10.1016/s0140-6736(07)60716-8 · Cited by 833
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
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
Tirona, R. G., Leake, B. F., Merino, G., & Kim, R. B. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103792200 · Cited by 625
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
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
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
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
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 154
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 135
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
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
Mulder, A. B. (2001) · Clinical Pharmacology & Therapeutics · doi:10.1067/mcp.2001.120251 · Cited by 92
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
CYP2D6*4 polymorphism is associated with statin-induced muscle effects
Frudakis, T. N., Thomas, M. J., Ginjupalli, S. N., Handelin, B., Gabriel, R., & Gomez, H. J. (2007) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0b013e328012d0a9 · Cited by 82
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
Flagged first, then by citations
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
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
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
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
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
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
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
