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<meta name="keywords" content="CN128903, sign or symptom, simvastatin response, slco1b1, zocor response, autosomal dominant, autosomal recessive, birth defects, chromosomal disease, chromosome, clinical features, clinical findings, clinical genetics, clinical recommendations, clinvar, congenital chromosomal disease, consumer genetic resources, cytogenetic location, disease characteristics, disease definitions, disease descriptions, disease ontology, disease synonyms, disease vocabulary, dysmorphology, entrez, familial disease, gene, gene-disease relationship, genereviews, genetic disease, genetic disorder, genetic terminology, genetic testing registry, genetics home reference, genomic disease, gtr, hereditary disease, heritable disease, hpo, human phenotype ontology, inherited disease, management guidelines, maternal inheritance, medgen, medical genetics, medical subject headings, mesh, mitochondrial inheritance, mode of inheritance, national center for biotechnology information, national institutes of health, national library of medicine, ncbi, nih, nlm, omim, ordo, orphanet, paternal inheritance, phenome, position statements, professional practice guidelines, rare disease, reference sequence, refseq, snomed ct, syndrome, undiagnosed diseases, x-linked recessive" /><meta name="description" content="Statins are among the most commonly prescribed drugs in the world to treat hypercholesterolemia and prevent cardiovascular diseases. They effectively lower cholesterol levels by inhibiting the HMG-CoA reductase to reduce cholesterol synthesis. Though well tolerated in general, the most common statin side effect is statin-associated musculoskeletal symptoms (SAMS) which range from myalgia, myopathy to fatal rhabdomyolysis, especially when statins are administered at higher doses and with certain other medications. Genetic variations in genes encoding the statin transporters, SLCO1B1 and ABCG2, and metabolizing enzyme, CYP2C9, have been shown to affect systemic plasma concentrations of statins and are associated with increased risk for SAMS. Guidelines regarding the use of pharmacogenomic tests in dosing for statins have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the CPIC and PharmGKB websites. The CPIC guideline provides specific therapeutic recommendations for simvastatin, atorvastatin, lovastatin, pravastatin and pitavastatin based on SLCO1B1 phenotype; rosuvastatin based on SLCO1B1 and ABCG2 phenotypes; and fluvastatin based on SLCO1B1 and CYP2C9 phenotypes. It serves as a guide for selecting the most appropriate statin and the optimal dose if pharmacogenetic test results are available." /><meta name="robots" content="index,nofollow,noarchive" />
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<!--
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UID=472073
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ConceptID=CN128903
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-->
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<!--imgCountBooks = 0--><h1 class="medgenTitle"><div class="MedGenTitleText">Simvastatin response</div></h1><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>472073</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier assigned by MedGen (starting with CN) for terms that cannot be identified in NLM's Unified Medical Language system (UMLS) Click for more information."><span class="highlight" style="background-color:">CN128903</span></a></dd><dt><span class="dotprefix"> •</span></dt><dd>Sign or Symptom</dd></dl></div></div><table class="medgenTable"><tbody><tr><td>Synonym:</td>
|
||
<td>Zocor response</td></tr>
|
||
<tr><td>Drug:</td>
|
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<td>
|
||
<div class="divPopper rprt" id="drug_22968"><div><strong>simvastatin</strong><div class="aux"><div class="resc"><dl class="rprtid"><dt>MedGen UID: </dt><dd>22968</dd><dt><span class="dotprefix"> •</span>Concept ID: </dt><dd><a href="/medgen/docs/help/#sources" target="_blank" title="Concept Unique Identifier from NLM's Unified Medical Language system (UMLS) Click for more information.">C0074554</a></dd><dt><span class="dotprefix"> •</span></dt><dd>Pharmacologic Substance</dd></dl></div></div></div>
|
||
<div class="spaceAbove">A lipid-lowering agent derived synthetically from a fermentation product of the fungus Aspergillus terreus. Hydrolyzed in vivo to an active metabolite, simvastatin competitively inhibits hepatic hydroxymethyl-glutaryl coenzyme A (HMG-CoA) reductase, the enzyme which catalyzes the conversion of HMG-CoA to mevalonate, a key step in cholesterol synthesis. This agent lowers plasma cholesterol and lipoprotein levels, and modulates immune responses by suppressing MHC II (major histocompatibility complex II) on interferon gamma-stimulated, antigen-presenting cells such as human vascular endothelial cells. (NCI04) [from NCI]</div></div>
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<div class="hangingIndent"><a title="click for more information" class="jig-ncbipopper" href="#drug_22968" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">simvastatin</a></div></td></tr>
|
||
<tr><td colspan="2" class="small"> </td></tr><tr><td><a class="help jig-ncbi-popper" data-jig="ncbipopper" href="#target-gene-loc">Gene (location):<img class="pulldown" src="//static.pubmed.gov/portal/portal3rc.fcgi/4223267/img/4204968" /></a><div class="display-none" id="target-gene-loc">
|
||
Gene(s) directly associated with<br />
|
||
this condition or phenotype.</div></td>
|
||
<td><a target="_blank" title="SLCO1B1 - ID: 10599 - NCBI Gene" href="/gene/10599" class="medgenPMinfo">SLCO1B1</a> (12p12.1)</td></tr>
|
||
</tbody></table></div><div class="rprt-body jig-ncbiinpagenav" data-jigconfig="smoothScroll: false, gotoTopLink: true, gotoTopLinkText: '', gotoTopLinkAttrs: {'title': 'Go to the top of the page'},allHeadingLevels: ['h1'], topOfPageTOC: true, tocId: 'my-toc'"><div id="rprt-tabs-1" class="rprt-tab"><div id="tb-termsProp-1"><div class="leftCol mgCol"><div>
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<div class="portlet mgSection" id="ID_100">
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<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Definition">Definition</h1><a sid="100" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
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||
<div class="portlet_content ln">Statins are among the most commonly prescribed drugs in the world to treat hypercholesterolemia and prevent cardiovascular diseases. They effectively lower cholesterol levels by inhibiting the HMG-CoA reductase to reduce cholesterol synthesis. Though well tolerated in general, the most common statin side effect is statin-associated musculoskeletal symptoms (SAMS) which range from myalgia, myopathy to fatal rhabdomyolysis, especially when statins are administered at higher doses and with certain other medications. Genetic variations in genes encoding the statin transporters, SLCO1B1 and ABCG2, and metabolizing enzyme, CYP2C9, have been shown to affect systemic plasma concentrations of statins and are associated with increased risk for SAMS. Guidelines regarding the use of pharmacogenomic tests in dosing for statins have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the CPIC and PharmGKB websites. The CPIC guideline provides specific therapeutic recommendations for simvastatin, atorvastatin, lovastatin, pravastatin and pitavastatin based on SLCO1B1 phenotype; rosuvastatin based on SLCO1B1 and ABCG2 phenotypes; and fluvastatin based on SLCO1B1 and CYP2C9 phenotypes. It serves as a guide for selecting the most appropriate statin and the optimal dose if pharmacogenetic test results are available. [from <a title="The Pharmacogenomics Knowledge Base" href="http://www.pharmgkb.org" class="defSource" target="_blank">PharmGKB</a>]</div>
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</div>
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<div class="portlet mgSection" id="ID_117">
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<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Additional_description">Additional description</h1><a sid="117" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
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||
<div class="portlet_content ln"><div class="mgSection"><strong>From Medical Genetics Summaries</strong><br />Simvastatin is a member of the statin class of drugs, used to regulate low-density lipoprotein (LDL) cholesterol levels in various conditions, including familial hypercholesterolemia (FH), primary hyperlipidemia, hypertriglyceridemia, and primary dysbetalipoproteinemia. Statins are also used to reduce total mortality risk associated with coronary heart disease, non-fatal myocardial infarction, and revascularization procedures in adults at high risk of coronary heart disease events, including those with established vascular disease or diabetes. Approved by the US FDA for use primarily in adults, simvastatin is also approved for children aged 10 and older to manage FH. Administered as a pro-drug, simvastatin must be metabolized to simvastatin acid, which then acts in the liver and other tissues to reduce cholesterol production by competitively inhibiting HMG-CoA reductase (3-hydroxy-methylglutaryl-coenzyme). Simvastatin acid also promotes an increase in the uptake of LDL from the bloodstream, resulting in a reduction in cardiovascular risk and improved health outcomes for most individuals. However, individuals can experience adverse reactions; the most common are statin-associated musculoskeletal symptoms (SAMS) or other serious reactions.
|
||
The Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group (DPWG) of the Royal Dutch Association for the Advancement of Pharmacy indicate that individuals with decreased function in the organic anion transporting polypeptides 1B1 (OATP1B1) hepatic transport enzyme (encoded by the SLCO1B1 gene) have an increased risk of SAMS. The CPIC guidelines provide dosing recommendations based on an individual’s predicted phenotype, stating that individuals with decreased or poor metabolizer phenotypes should be prescribed an alternative statin or a lower dose of simvastatin. Criteria for choosing the relative potency of an alternative statin or the dose of simvastatin are also outlined by CPIC. The DPWG guidelines focus on the most common functional variant, a single nucleotide variation (SNV) at rs4149056, NM_006446.5:c.521T>C, recommending that individuals heterozygous or homozygous for the variant allele, resulting in decreased or poor function phenotype, choose an alternative statin. The US FDA does not specifically address SLCO1B1 genetic variation in the simvastatin drug label, but it does discuss various medications that are either contraindicated (strong cytochrome P450 enzyme 3A4 [CYP3A4] inhibitors, gemfibrozil, cyclosporin and danazol) with simvastatin or may increase the risk of myopathy. The drug label for simvastatin in Switzerland, however, describes the increased risk of SAMS for individuals who have at least one variant allele at rs4149056, and recommends considering genotyping results indicating a CC genotype at this SNV during risk-benefit assessment before prescribing 80 mg doses of simvastatin due to higher myopathy risks. The interplay of genetics, co-medications, comorbidities, and simvastatin dose highlights the complex factors that contribute to an individual's risk of developing SAMS. <a target="_blank" href="https://www.ncbi.nlm.nih.gov/books/NBK602238">https://www.ncbi.nlm.nih.gov/books/NBK602238</a></div></div>
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</div>
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<div class="portlet mgSection" id="ID_118">
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<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Term_Hierarchy">Term Hierarchy</h1><a sid="118" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
|
||
<div class="portlet_content ln HierarchyGTR"><div class="jig-ncbitabs"><ul><li><a href="#tabGTR">GTR</a></li><li><a href="#tabMGEN">MeSH</a></li></ul><div id="tabGTR"><div class="search_result"><div class="rprts"><div class="chiclet_legend"><span class="chiclet_list" style="position:static;"><span title="Clinical test" class="chiclet Ccolor round">C</span><span>Clinical test, </span><span title="Research test" class="chiclet Rcolor round">R</span><span>Research test, </span><span title="OMIM" class="chiclet Ocolor ">O</span><span>OMIM, </span><span title="GeneReview" class="chiclet Gcolor">G</span><span><em>GeneReviews</em>, </span><span title="ClinVar" class="chiclet Vcolor">V</span><span>ClinVar </span></span></div><div id="hierarchy" class="margin_t1"><div class="ds_tree"><ul><li class="TLclosed"><span class="chiclet_list"><span class="chiclet Ccolor round" title="Clinical test"><a target="_blank" href="/gtr/tests/?term=C0570410[DISCUI]&test_type=Clinical" ref="ncbi_uid=654187">C</a></span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet unavailable" title="OMIM">O</span><span class="chiclet unavailable" title="GeneReviews">G</span><span class="chiclet unavailable" title="ClinVar">V</span></span><span class="TLline"><a href="/medgen/654187" ref="tree=GTR&ncbi_uid=654187&link_uid=654187" title="View MedGen record for 'Statin causing adverse effect in therapeutic use'">Statin causing adverse effect in therapeutic use</a></span><ul><li class="TLclosed"><span class="chiclet_list"><span class="chiclet Ccolor round" title="Clinical test"><a target="_blank" href="/gtr/tests/?term=CN077961[DISCUI]&test_type=Clinical" ref="ncbi_uid=450433">C</a></span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet unavailable" title="OMIM">O</span><span class="chiclet unavailable" title="GeneReviews">G</span><span class="chiclet Vcolor" title="ClinVar"><a target="_blank" href="/clinvar?LinkName=medgen_clinvar&from_uid=450433" ref="ncbi_uid=450433">V</a></span></span><span class="TLline"><a href="/medgen/450433" ref="tree=GTR&ncbi_uid=450433&link_uid=450433" title="View MedGen record for 'Atorvastatin response'">Atorvastatin response</a></span></li><li class="matched_ds"><span class="chiclet_list"><span class="chiclet Ccolor round" title="Clinical test"><a target="_blank" href="/gtr/tests/?term=CN128903[DISCUI]&test_type=Clinical" ref="ncbi_uid=472073">C</a></span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet unavailable" title="OMIM">O</span><span class="chiclet unavailable" title="GeneReviews">G</span><span class="chiclet unavailable" title="ClinVar">V</span></span><span class="TLline">Simvastatin response</span></li><li class="TLclosed"><span class="chiclet_list"><span class="chiclet Ccolor round" title="Clinical test"><a target="_blank" href="/gtr/tests/?term=C5923430[DISCUI]&test_type=Clinical" ref="ncbi_uid=1857639">C</a></span><span class="chiclet unavailable round" title="Research Tests">R</span><span class="chiclet unavailable" title="OMIM">O</span><span class="chiclet unavailable" title="GeneReviews">G</span><span class="chiclet unavailable" title="ClinVar">V</span></span><span class="TLline"><a href="/medgen/1857639" ref="tree=GTR&ncbi_uid=1857639&link_uid=1857639" title="View MedGen record for 'Statin-induced myopathy'">Statin-induced myopathy</a></span></li></ul></li></ul></div></div></div></div></div><div id="tabMGEN"><div class="ds_tree"><ul><li><span class="TLline"><a href="/medgen/654187" ref="tree=MeSH" title="MedGen record for Statin causing adverse effect in therapeutic use">Statin causing adverse effect in therapeutic use</a></span><ul><li><span class="matched_ds">Simvastatin response</span></li></ul></li></ul></div></div></div></div>
|
||
</div>
|
||
|
||
<div class="portlet mgSection" id="ID_105">
|
||
<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Professional_guidelines">Professional guidelines</h1><a sid="105" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
|
||
<div class="portlet_content ln"><h3 class="subhead">PubMed<a class="help jig-ncbi-popper" data-jig="ncbipopper" href="#guidelinesHelpPM"><img class="pulldown" src="//static.pubmed.gov/portal/portal3rc.fcgi/4223267/img/4204968" /></a></h3>
|
||
<div class="nl"><a target="_blank" href="/pubmed/32729746">An updated review of pharmacokinetic drug interactions and pharmacogenetics of statins.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Hirota T,
|
||
Fujita Y,
|
||
Ieiri I</span><br />
|
||
<span class="medgenPMjournal">Expert Opin Drug Metab Toxicol</span>
|
||
2020 Sep;16(9):809-822.
|
||
Epub 2020 Aug 6
|
||
doi: 10.1080/17425255.2020.1801634.
|
||
<span class="bold">PMID: </span><a href="/pubmed/32729746" target="_blank">32729746</a></div>
|
||
|
||
<div class="nl"><a target="_blank" href="/pubmed/31038898">Clinically Relevant Drug-Drug Interactions in Primary Care.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Carpenter M,
|
||
Berry H,
|
||
Pelletier AL</span><br />
|
||
<span class="medgenPMjournal">Am Fam Physician</span>
|
||
2019 May 1;99(9):558-564.
|
||
<span class="bold">PMID: </span><a href="/pubmed/31038898" target="_blank">31038898</a></div>
|
||
|
||
<div class="nl"><a target="_blank" href="/pubmed/30845106">Lipid-lowering drugs.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMjournal">Med Lett Drugs Ther</span>
|
||
2019 Feb 11;61(1565):17-24.
|
||
<span class="bold">PMID: </span><a href="/pubmed/30845106" target="_blank">30845106</a></div>
|
||
<div><a target="_blank" href="https://pubmed.ncbi.nlm.nih.gov/?term=(%22simvastatin%22%5Btiab%3A~0%5D)%20AND%20(%22english%20and%20humans%22%5BFilter%5D)%20AND%20(%20(%22practice%20guideline%22%5BFilter%5D)%20OR%20(practice*%5Btitl%5D%20AND%20(guideline%5Btitl%5D%20OR%20parameter%5Btitl%5D%20OR%20resource%5Btitl%5D%20OR%20bulletin%5Btitl%5D%20OR%20best%5Btitl%5D))%20OR%20(genetic*%5Btitl%5D%20AND%20(evaluation%5Btitl%5D%20OR%20counseling%5Btitl%5D%20OR%20screening%5Btitl%5D%20OR%20test*%5Btitl%5D))%20OR%20(clinical%5Btitl%5D%20AND%20((expert%5Btitl%5D%20AND%20consensus%5Btitl%5D)%20OR%20utility%5Btitl%5D%20OR%20guideline*%5Btitl%5D))%20OR%20(management%5Btitl%5D%20AND%20(clinical%5Btitl%5D%20OR%20diagnos*%5Btitl%5D%20OR%20recommendation%5Btitl%5D%20OR%20pain%5Btitl%5D%20OR%20surveillance%5Btitl%5D%20OR%20emergency%5Btitl%5D%20OR%20guideline*%5Btitl%5D%20OR%20therap*))%20OR%20(treatment%5Btitl%5D%20AND%20((evaluation%5Btitl%5D%20AND%20diagnosis%5Btitl%5D)%20OR%20(assessment%5Btitl%5D%20AND%20prevention%5Btitl%5D)%20OR%20therap*))%20OR%20(Diagnos*%5Btitl%5D%20AND%20(prenatal%5Btitl%5D%20OR%20treatment%5Btitl%5D%20OR%20follow-up%5Btitl%5D%20OR%20statement%5Btitl%5D%20OR%20criteria%5Btitl%5D%20OR%20newborn%5Btitl%5D%20OR%20differential%5Btitl%5D%20OR%20neonatal%5Btitl%5D%20OR%20neonate%5Btitl%5D))%20OR%20(guideline*%5Btitl%5D%20AND%20(pharmacogenetic*%5Btitl%5D%20OR%20recommendation%5Btitl%5D%20OR%20therap*%5Btitl%5D%20OR%20evidence-based%5Btitl%5D%20OR%20consensus%5Btitl%5D%20OR%20(technical%5Btitl%5D%20AND%20standard*%5Btitl%5D)%20OR%20(molecular%5Btitl%5D%20AND%20testing%5Btitl%5D)))%20OR%20(risk%5Btitl%5D%20AND%20assessment%5Btitl%5D)%20OR%20(recommendation*%5Btitl%5D%20AND%20(statement%5Btitl%5D%20OR%20Evidence-based%5Btitl%5D%20OR%20Consensus%5Btitl%5D))%20OR%20(care%20AND%20((Patient%5Btitl%5D%20AND%20standard*%5Btitl%5D)%20OR%20primary%5Btitl%5D%20OR%20psychosocial%5Btitl%5D))%20OR%20(Health%5Btitl%5D%20AND%20supervision%5Btitl%5D)%20OR%20(statement%5Btitl%5D%20AND%20(policy%5Btitl%5D%20OR%20position%5Btitl%5D%20OR%20Consensus%5Btitl%5D))%20OR%20(pharmacogenetics%5Btitl%5D%20AND%20(Dosing%5Btitl%5D%20OR%20therap*%5Btitl%5D%20OR%20genotype*%5Btitl%5D%20OR%20drug*%5Btitl%5D))%20OR%20(Chemotherapy%5Btitl%5D%20AND%20decision*%5Btitl%5D)%20OR%20(screening%5Btitl%5D%20AND%20(newborn%5Btitl%5D%20OR%20neonat*%5Btitl%5D%20OR%20detection%5Btitl%5D%20OR%20diagnos*%5Btitl%5D))%20OR%20(criteria%5Btitl%5D%20OR%20genotype*%5Btitl%5D)%20)%20NOT%20(%22Case%20reports%22%5BPublication%20type%5D%20OR%20%22clinical%20study%22%5BPublication%20Type%5D%20OR%20%22randomized%20controlled%20trial%22%5BPublication%20Type%5D)" title="PubMed search">See all (462)</a></div></div>
|
||
</div>
|
||
<div class="display-none help-popup" id="guidelinesHelpPM">These guidelines are articles in PubMed that match specific search criteria developed by MedGen to capture the most relevant practice guidelines. This list may not be comprehensive and may include broader topics as well. See the <a href="/medgen/docs/faq/" title="Frequently asked questions" target="_blank">FAQ</a> for details.</div><div class="display-none help-popup" id="guidelinesHelpCurated">These guidelines are manually curated by the MedGen team
|
||
to supplement articles available in PubMed. See the <a href="/medgen/docs/faq/" title="Frequently asked questions" target="_blank">FAQ</a> for details.</div>
|
||
<div class="portlet mgSection" id="ID_103">
|
||
<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Recent_clinical_studies">Recent clinical studies</h1><a sid="103" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
|
||
<div class="portlet_content ln"><h3 class="subhead">Etiology</h3>
|
||
<div class="nl"><a target="_blank" href="/pubmed/34403130">Pharmacogenomics of statins: lipid response and other outcomes in Brazilian cohorts.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Dagli-Hernandez C,
|
||
Zhou Y,
|
||
Lauschke VM,
|
||
Genvigir FDV,
|
||
Hirata TDC,
|
||
Hirata MH,
|
||
Hirata RDC</span><br />
|
||
<span class="medgenPMjournal">Pharmacol Rep</span>
|
||
2022 Feb;74(1):47-66.
|
||
Epub 2021 Aug 17
|
||
doi: 10.1007/s43440-021-00319-y.
|
||
<span class="bold">PMID: </span><a href="/pubmed/34403130" target="_blank">34403130</a></div>
|
||
|
||
<div class="nl"><a target="_blank" href="/pubmed/28851085">The effect of APOE, CETP, and PCSK9 polymorphisms on simvastatin response in Thai hypercholesterolemic patients.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Wanmasae S,
|
||
Sirintronsopon W,
|
||
Porntadavity S,
|
||
Jeenduang N</span><br />
|
||
<span class="medgenPMjournal">Cardiovasc Ther</span>
|
||
2017 Dec;35(6)
|
||
Epub 2017 Sep 25
|
||
doi: 10.1111/1755-5922.12302.
|
||
<span class="bold">PMID: </span><a href="/pubmed/28851085" target="_blank">28851085</a></div>
|
||
<div><a target="_blank" href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Simvastatin%20response%22%20AND%20Etiology%2Fbroad%5Bfilter%5D%20%20AND%20%22english%20and%20humans%22%5Bfilter%5D%20NOT%20comment%5BPTYP%5D%20NOT%20letter%5BPTYP%5D" title="PubMed search">See all (2)</a></div><h3 class="subhead">Therapy</h3>
|
||
<div class="nl"><a target="_blank" href="/pubmed/29427701">Statins differentially modulate microRNAs expression in peripheral cells of hyperlipidemic subjects: A pilot study.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Zambrano T,
|
||
Hirata RDC,
|
||
Hirata MH,
|
||
Cerda Á,
|
||
Salazar LA</span><br />
|
||
<span class="medgenPMjournal">Eur J Pharm Sci</span>
|
||
2018 May 30;117:55-61.
|
||
Epub 2018 Feb 7
|
||
doi: 10.1016/j.ejps.2018.02.007.
|
||
<span class="bold">PMID: </span><a href="/pubmed/29427701" target="_blank">29427701</a></div>
|
||
|
||
<div class="nl"><a target="_blank" href="/pubmed/28851085">The effect of APOE, CETP, and PCSK9 polymorphisms on simvastatin response in Thai hypercholesterolemic patients.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Wanmasae S,
|
||
Sirintronsopon W,
|
||
Porntadavity S,
|
||
Jeenduang N</span><br />
|
||
<span class="medgenPMjournal">Cardiovasc Ther</span>
|
||
2017 Dec;35(6)
|
||
Epub 2017 Sep 25
|
||
doi: 10.1111/1755-5922.12302.
|
||
<span class="bold">PMID: </span><a href="/pubmed/28851085" target="_blank">28851085</a></div>
|
||
|
||
<div class="nl"><a target="_blank" href="/pubmed/28482130">Candidate-Gene Study of Functional Polymorphisms in SLCO1B1 and CYP3A4/5 and the Cholesterol-Lowering Response to Simvastatin.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Kitzmiller JP,
|
||
Luzum JA,
|
||
Dauki A,
|
||
Krauss RM,
|
||
Medina MW</span><br />
|
||
<span class="medgenPMjournal">Clin Transl Sci</span>
|
||
2017 May;10(3):172-177.
|
||
Epub 2016 Nov 4
|
||
doi: 10.1111/cts.12432.
|
||
<span class="bold">PMID: </span><a href="/pubmed/28482130" target="_blank">28482130</a><a href="/pmc/articles/PMC5421731" target="_blank" class="PubMedFree">Free PMC Article</a></div>
|
||
<div><a target="_blank" href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Simvastatin%20response%22%20AND%20Therapy%2Fbroad%5Bfilter%5D%20%20AND%20%22english%20and%20humans%22%5Bfilter%5D%20NOT%20comment%5BPTYP%5D%20NOT%20letter%5BPTYP%5D" title="PubMed search">See all (3)</a></div><h3 class="subhead">Prognosis</h3>
|
||
<div class="nl"><a target="_blank" href="/pubmed/28482130">Candidate-Gene Study of Functional Polymorphisms in SLCO1B1 and CYP3A4/5 and the Cholesterol-Lowering Response to Simvastatin.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Kitzmiller JP,
|
||
Luzum JA,
|
||
Dauki A,
|
||
Krauss RM,
|
||
Medina MW</span><br />
|
||
<span class="medgenPMjournal">Clin Transl Sci</span>
|
||
2017 May;10(3):172-177.
|
||
Epub 2016 Nov 4
|
||
doi: 10.1111/cts.12432.
|
||
<span class="bold">PMID: </span><a href="/pubmed/28482130" target="_blank">28482130</a><a href="/pmc/articles/PMC5421731" target="_blank" class="PubMedFree">Free PMC Article</a></div>
|
||
<div><a target="_blank" href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Simvastatin%20response%22%20AND%20Prognosis%2Fbroad%5Bfilter%5D%20%20AND%20%22english%20and%20humans%22%5Bfilter%5D%20NOT%20comment%5BPTYP%5D%20NOT%20letter%5BPTYP%5D" title="PubMed search">See all (1)</a></div><h3 class="subhead">Clinical prediction guides</h3>
|
||
<div class="nl"><a target="_blank" href="/pubmed/28482130">Candidate-Gene Study of Functional Polymorphisms in SLCO1B1 and CYP3A4/5 and the Cholesterol-Lowering Response to Simvastatin.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Kitzmiller JP,
|
||
Luzum JA,
|
||
Dauki A,
|
||
Krauss RM,
|
||
Medina MW</span><br />
|
||
<span class="medgenPMjournal">Clin Transl Sci</span>
|
||
2017 May;10(3):172-177.
|
||
Epub 2016 Nov 4
|
||
doi: 10.1111/cts.12432.
|
||
<span class="bold">PMID: </span><a href="/pubmed/28482130" target="_blank">28482130</a><a href="/pmc/articles/PMC5421731" target="_blank" class="PubMedFree">Free PMC Article</a></div>
|
||
|
||
<div class="nl"><a target="_blank" href="/pubmed/14630613">Cytoskeletal activation and altered gene expression in endothelial barrier regulation by simvastatin.</a></div>
|
||
<div class="portlet_content ln"><span class="medgenPMauthor">Jacobson JR,
|
||
Dudek SM,
|
||
Birukov KG,
|
||
Ye SQ,
|
||
Grigoryev DN,
|
||
Girgis RE,
|
||
Garcia JG</span><br />
|
||
<span class="medgenPMjournal">Am J Respir Cell Mol Biol</span>
|
||
2004 May;30(5):662-70.
|
||
Epub 2003 Nov 20
|
||
doi: 10.1165/rcmb.2003-0267OC.
|
||
<span class="bold">PMID: </span><a href="/pubmed/14630613" target="_blank">14630613</a></div>
|
||
<div><a target="_blank" href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Simvastatin%20response%22%20AND%20Clinical%20prediction%20guides%2Fbroad%5Bfilter%5D%20%20AND%20%22english%20and%20humans%22%5Bfilter%5D%20NOT%20comment%5BPTYP%5D%20NOT%20letter%5BPTYP%5D" title="PubMed search">See all (2)</a></div></div>
|
||
</div>
|
||
|
||
<div class="portlet mgSection" id="ID_120">
|
||
<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Therapeutic_recommendations">Therapeutic recommendations</h1><a sid="120" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
|
||
<div class="portlet_content ln" id="therapeutic"><strong>From <a href="https://www.ncbi.nlm.nih.gov/books/NBK602238" target="_blank">Medical Genetics Summaries</a></strong><br /><div id="TheraputicContent"><div class="divPopper rprt" id="simvastatin_REF_1" style="display: none;">1. SIMVASTATIN- simvastatin tablet.
|
||
Somerset, NJ, USA: Micro Labs Limited; 2023. 'Available from:' <a href="https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5c1c694c-4b08-469e-b538-08e69df06146" target="_blank">https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5c1c694c-4b08-469e-b538-08e69df06146</a>.</div><div class="divPopper rprt" id="simvastatin_REF_2" style="display: none;">2. Cooper-DeHoff,
|
||
R.M., et
|
||
al., The Clinical Pharmacogenetics
|
||
Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9
|
||
genotypes and Statin-Associated Musculoskeletal
|
||
Symptoms.
|
||
Clin Pharmacol Ther, 2022.
|
||
111(5): p.
|
||
1007-1021.
|
||
</div><div class="divPopper rprt" id="simvastatin_REF_3" style="display: none;">3. Pharmacogenetic Recommendation Text
|
||
[Cited 11 Dec 2023]. Available from <a href="https://www.knmp.nl/dossiers/farmacogenetica" target="_blank">https://www.knmp.nl/dossiers/farmacogenetica</a>.</div><p><b>This section contains excerpted</b>
|
||
<sup>1</sup>
|
||
<b>information on gene-based dosing recommendations. Neither this section nor
|
||
other parts of this review contain the complete recommendations from the
|
||
sources.</b>
|
||
</p><p><b>2023 Statement from the US Food and Drug Administration (FDA):</b>
|
||
</p><p>Warnings and Precautions- Myopathy and Rhabdomyolysis</p><p>Simvastatin may cause myopathy and rhabdomyolysis… Risk factors for
|
||
myopathy include age 65 years or greater, uncontrolled hypothyroidism, renal
|
||
impairment, concomitant use with certain other drugs (including other lipid
|
||
lowering therapies), and higher simvastatin dosage; Chinese patients on
|
||
simvastatin may be at higher risk for myopathy…The risk of myopathy is
|
||
increased by elevated plasma levels of simvastatin and simvastatin acid. The
|
||
risk is also greater in patients taking an 80 mg daily dosage of simvastatin
|
||
compared with patients taking lower simvastatin tablets dosages and compared
|
||
with patients using other statins with similar or greater LDL-C lowering
|
||
efficacy.</p><p>Steps to Prevent or Reduce the Risk of Myopathy and Rhabdomyolysis</p><p>The concomitant use of strong CYP3A4 inhibitors with simvastatin is
|
||
contraindicated. If short-term treatment with strong CYP3A4 inhibitors is
|
||
required, temporarily suspend simvastatin during the duration of strong CYP3A4
|
||
inhibitor treatment. The concomitant use of simvastatin with gemfibrozil,
|
||
cyclosporine, or danazol is also contraindicated … Simvastatin dosage
|
||
modifications are recommended for patients taking lomitapide, verapamil,
|
||
diltiazem, dronedarone, amiodarone, amlodipine or ranolazine.</p><p><b>Please review the complete therapeutic recommendations that are located
|
||
here:</b>
|
||
(<a title="click for more information" class="jig-ncbipopper s_TOP" href="#simvastatin_REF_1" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">1</a>)</p><h2>2022 Statement from the Clinical Pharmacogenetics Implementation Consortium (CPIC):</h2><p>Phenotype: SLCO1B1 decreased function or SLCO1B1 possible decreased
|
||
function</p><p>Implications: Increased simvastatin acid exposure as compared with normal
|
||
function; increased risk of myopathy.</p><p>Dosing recommendation: Prescribe an alternative statin depending on the
|
||
desired potency (see Figure
|
||
1 for recommendations for alternative statins). If simvastatin
|
||
therapy is warranted, limit dose to <20 mg/day.</p><p>Phenotype: SLCO1B1 poor function</p><p>Implications: Increased simvastatin acid exposure compared with normal and
|
||
decreased function; highly increased myopathy risk.</p><p>Dosing recommendation: Prescribe an alternative statin depending on the
|
||
desired potency (see Figure
|
||
1 for recommendations for alternative statins)</p><p><b>Please review the complete therapeutic recommendations that are located
|
||
here:</b>
|
||
(<a title="click for more information" class="jig-ncbipopper s_TOP" href="#simvastatin_REF_2" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">2</a>)</p><h2>2020 Summary of recommendations from the Dutch Pharmacogenetics Working Group (DPWG) of the Royal Dutch Association for the Advancement of Pharmacy (KNMP)</h2><p>SLCO1B1 521CC: [simvastatin]</p><p>When using simvastatin 80 mg/day, the risk of myopathy is increased 30-fold
|
||
to 18% and the risk of severe myopathy is increased 48-fold to 12%. When
|
||
using 40 mg/day, this risk is increased 7-fold to 1% and 11-fold to 0.68%
|
||
respectively. The gene variation leads to reduced simvastatin transport to
|
||
the liver, which increases the simvastatin plasma concentration and
|
||
therefore the risk of side effects.</p><p>1. Choose an alternative</p><p>Consider any additional risk factors for statin-induced myopathy.</p><p>Atorvastatin is affected less severely by the SLCO1B1 gene variation, but is
|
||
also affected by CYP3A4 inhibitors such as amiodarone, verapamil and
|
||
diltiazem. Use of atorvastatin is not recommended for patients with
|
||
additional risk factors for statin-induced myopathy.</p><p>Rosuvastatin and pravastatin are influenced to a lesser extent by the SLCO1B1
|
||
gene variation. They are also not influenced by CYP3A4 inhibitors such as
|
||
amiodarone, verapamil and diltiazem.</p><p>Fluvastatin is not significantly influenced by the SLCO1B1 gene variation or
|
||
CYP3A4 inhibitors.</p><p>SLCO1B1 521TC: [simvastatin]</p><p>When using simvastatin 80 mg/day, the risk of myopathy is increased 5-fold to
|
||
3% for moderately severe to severe myopathy and 1.3% for severe myopathy.
|
||
When using 40 mg/day, this risk is increased 2.6-fold to 0.39% and 0.17%
|
||
respectively. The gene variation may lead to reduced simvastatin transport
|
||
to the liver, which may increase simvastatin plasma concentrations and
|
||
therefore the risk of side effects.</p><p>1. Choose an alternative</p><p>Consider any additional risk factors for statin-induced myopathy.</p><p>Atorvastatin is affected less severely by the SLCO1B1 gene variation, but is
|
||
also affected by CYP3A4 inhibitors such as amiodarone, verapamil and
|
||
diltiazem. Use of atorvastatin is not recommended for patients with
|
||
additional risk factors for statin-induced myopathy.</p><p>Rosuvastatin and pravastatin are influenced to a lesser extent by the SLCO1B1
|
||
gene variation. They are also not influenced by CYP3A4 inhibitors such as
|
||
amiodarone, verapamil and diltiazem.</p><p>Fluvastatin is not significantly influenced by the SLCO1B1 gene variation or
|
||
CYP3A4 inhibitors.</p><p>2. If an alternative is not an option:</p><p>1. Avoid simvastatin doses exceeding 40 mg/day (for example, by adding
|
||
ezetimibe)<sup>a</sup>
|
||
</p><p>2. Advise the patient to report muscle symptoms. <sup>a</sup>
|
||
</p><p><b>Please review the complete therapeutic recommendations that are located
|
||
here:</b>
|
||
(<a title="click for more information" class="jig-ncbipopper s_TOP" href="#simvastatin_REF_3" data-jigconfig="hasArrow: true, openEvent: 'click', closeEvent: 'mouseout', openAnimation: 'fadeIn', closeAnimation: 'fadeOut', triggerPosition: 'center right', destPosition: 'center left', arrowDirection: 'left'">3</a>)
|
||
<sup>a</sup>
|
||
Note that minor variations in wording versus the cited
|
||
guidelines are included here based on personal communication from DPWG.</p><p><sup>1</sup>
|
||
|
||
The FDA has distinct labels for specific drug formulations. We have
|
||
substituted the generic names for any drug labels in this excerpt. The FDA
|
||
may not have labeled all formulations containing the generic drug. Certain
|
||
terms, genes and genetic variants may be corrected in accordance with
|
||
nomenclature standards, where necessary. We have given the full name of
|
||
abbreviations, shown in square brackets, where necessary.</p></div></div>
|
||
</div>
|
||
</div></div></div></div></div></div></div>
|
||
<div id="messagearea_bottom">
|
||
|
||
</div>
|
||
<div class=" bottom">
|
||
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
<div class="supplemental col three_col last">
|
||
<h2 class="offscreen_noflow">Supplemental Content</h2>
|
||
|
||
<div>
|
||
|
||
<!-- MedGen supplemental column starts here -->
|
||
<div class="rightCol mgCol">
|
||
<div class="portlet mgSection" id="ID_113">
|
||
<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Table_of_contents">Table of contents</h1><a sid="113" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
|
||
<div class="portlet_content ln"><ul id="my-toc"></ul></div>
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|
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|
||
<div class="portlet mgSection" id="ID_106">
|
||
<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Genetic_Testing_Registry">Genetic Testing Registry</h1><a sid="106" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
|
||
<div class="portlet_content ln"><ul><li><a href="/gtr/tests?term=CN128903%5bDISCUI%5d&filter=method%3A2%5F8" target="_blank">Deletion/duplication analysis (5)</a></li>
|
||
<li><a href="/gtr/tests?term=CN128903%5bDISCUI%5d&filter=method%3A2%5F17" target="_blank">Mutation scanning of the entire coding region (1)</a></li>
|
||
<li><a href="/gtr/tests?term=CN128903%5bDISCUI%5d&filter=method%3A2%5F19" target="_blank">Targeted variant analysis (13)</a></li>
|
||
<li class="portletSeeAll portletSeeAllPad"><total><a href="/gtr/tests?term=CN128903%5bDISCUI%5d" target="_blank">See all (14)</a></total></li>
|
||
</ul></div>
|
||
</div>
|
||
|
||
<div class="portlet mgSection" id="ID_119">
|
||
<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Clinical_resources">Clinical resources</h1><a sid="119" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
|
||
<div class="portlet_content ln"><ul><li><a href="https://www.pharmgkb.org/chemical/PA451363" target="_blank">PharmGKB</a></li><li><a href="https://clinicaltrials.gov/search?cond=Simvastatin%20response" target="_blank">ClinicalTrials.gov</a></li></ul></div>
|
||
</div>
|
||
|
||
<div class="portlet mgSection" id="ID_121">
|
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<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Practice_guidelines">Practice guidelines</h1><a sid="121" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
|
||
<div class="portlet_content ln"><ul class="a_poppers"><li><a target="_blank" href="https://pubmed.ncbi.nlm.nih.gov/?term=(%22simvastatin%22%5Btiab%3A~0%5D)%20AND%20(%22english%20and%20humans%22%5BFilter%5D)%20AND%20(%20(%22practice%20guideline%22%5BFilter%5D)%20OR%20(practice*%5Btitl%5D%20AND%20(guideline%5Btitl%5D%20OR%20parameter%5Btitl%5D%20OR%20resource%5Btitl%5D%20OR%20bulletin%5Btitl%5D%20OR%20best%5Btitl%5D))%20OR%20(genetic*%5Btitl%5D%20AND%20(evaluation%5Btitl%5D%20OR%20counseling%5Btitl%5D%20OR%20screening%5Btitl%5D%20OR%20test*%5Btitl%5D))%20OR%20(clinical%5Btitl%5D%20AND%20((expert%5Btitl%5D%20AND%20consensus%5Btitl%5D)%20OR%20utility%5Btitl%5D%20OR%20guideline*%5Btitl%5D))%20OR%20(management%5Btitl%5D%20AND%20(clinical%5Btitl%5D%20OR%20diagnos*%5Btitl%5D%20OR%20recommendation%5Btitl%5D%20OR%20pain%5Btitl%5D%20OR%20surveillance%5Btitl%5D%20OR%20emergency%5Btitl%5D%20OR%20guideline*%5Btitl%5D%20OR%20therap*))%20OR%20(treatment%5Btitl%5D%20AND%20((evaluation%5Btitl%5D%20AND%20diagnosis%5Btitl%5D)%20OR%20(assessment%5Btitl%5D%20AND%20prevention%5Btitl%5D)%20OR%20therap*))%20OR%20(Diagnos*%5Btitl%5D%20AND%20(prenatal%5Btitl%5D%20OR%20treatment%5Btitl%5D%20OR%20follow-up%5Btitl%5D%20OR%20statement%5Btitl%5D%20OR%20criteria%5Btitl%5D%20OR%20newborn%5Btitl%5D%20OR%20differential%5Btitl%5D%20OR%20neonatal%5Btitl%5D%20OR%20neonate%5Btitl%5D))%20OR%20(guideline*%5Btitl%5D%20AND%20(pharmacogenetic*%5Btitl%5D%20OR%20recommendation%5Btitl%5D%20OR%20therap*%5Btitl%5D%20OR%20evidence-based%5Btitl%5D%20OR%20consensus%5Btitl%5D%20OR%20(technical%5Btitl%5D%20AND%20standard*%5Btitl%5D)%20OR%20(molecular%5Btitl%5D%20AND%20testing%5Btitl%5D)))%20OR%20(risk%5Btitl%5D%20AND%20assessment%5Btitl%5D)%20OR%20(recommendation*%5Btitl%5D%20AND%20(statement%5Btitl%5D%20OR%20Evidence-based%5Btitl%5D%20OR%20Consensus%5Btitl%5D))%20OR%20(care%20AND%20((Patient%5Btitl%5D%20AND%20standard*%5Btitl%5D)%20OR%20primary%5Btitl%5D%20OR%20psychosocial%5Btitl%5D))%20OR%20(Health%5Btitl%5D%20AND%20supervision%5Btitl%5D)%20OR%20(statement%5Btitl%5D%20AND%20(policy%5Btitl%5D%20OR%20position%5Btitl%5D%20OR%20Consensus%5Btitl%5D))%20OR%20(pharmacogenetics%5Btitl%5D%20AND%20(Dosing%5Btitl%5D%20OR%20therap*%5Btitl%5D%20OR%20genotype*%5Btitl%5D%20OR%20drug*%5Btitl%5D))%20OR%20(Chemotherapy%5Btitl%5D%20AND%20decision*%5Btitl%5D)%20OR%20(screening%5Btitl%5D%20AND%20(newborn%5Btitl%5D%20OR%20neonat*%5Btitl%5D%20OR%20detection%5Btitl%5D%20OR%20diagnos*%5Btitl%5D))%20OR%20(criteria%5Btitl%5D%20OR%20genotype*%5Btitl%5D)%20)%20NOT%20(%22Case%20reports%22%5BPublication%20type%5D%20OR%20%22clinical%20study%22%5BPublication%20Type%5D%20OR%20%22randomized%20controlled%20trial%22%5BPublication%20Type%5D)" title="PubMed search">PubMed</a><div class="help-popup">See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the <a href="/medgen/docs/faq/" title="Frequently asked questions" target="_blank">FAQ</a> for details.</div></li></ul></div>
|
||
</div>
|
||
|
||
<div class="portlet mgSection" id="ID_115">
|
||
<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Molecular_resources">Molecular resources</h1><a sid="115" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
|
||
<div class="portlet_content ln"><ul><li><a href="http://www.omim.org/search?index=entry&start=1&limit=10&sort=score%20desc&field=number&search=604843" target="_blank">OMIM</a></li><li><a href="/clinvar/?term=10599[geneid]" target="_blank">View SLCO1B1 variations in ClinVar</a></li><li><a href="/nuccore/225903422" target="_blank">RefSeqGene</a></li></ul></div>
|
||
</div>
|
||
|
||
<div class="portlet mgSection" id="ID_116">
|
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<div class="portlet_head mgSectionHead ui-widget-header"><h1 class="nl" id="Consumer_resources">Consumer resources</h1><a sid="116" href="#" class="portlet_shutter" title="Show/hide content"></a></div>
|
||
<div class="portlet_content ln"><ul><li><a href="https://vsearch.nlm.nih.gov/vivisimo/cgi-bin/query-meta?v:project=medlineplus&query=Simvastatin%20response" target="_blank">MedlinePlus</a></li></ul></div>
|
||
</div>
|
||
</div>
|
||
<div class="portlet brieflink">
|
||
<div class="portlet_head">
|
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<div class="portlet_title">
|
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<h3>Reviews</h3>
|
||
</div>
|
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|
||
</div>
|
||
<div class="portlet_content">
|
||
<ul>
|
||
<li>
|
||
<a href="/books/NBK602238" ref="ncbi_uid=&discoId=gtr_reviews&linkpos=1&linkpostotal=3" target="_blank">Medical Genetics Summaries</a>
|
||
</li>
|
||
<li>
|
||
<a href="/pubmed/clinical?term=Simvastatin%20response" ref="ncbi_uid=&discoId=gtr_reviews&linkpos=2&linkpostotal=3" target="_blank">PubMed Clinical Queries</a>
|
||
</li>
|
||
<li>
|
||
<a href="/pubmed?term=Simvastatin%20response%20AND%20humans[mesh]%20AND%20review[publication%20type]" ref="ncbi_uid=&discoId=gtr_reviews&linkpos=3&linkpostotal=3" target="_blank">Reviews in PubMed</a>
|
||
</li>
|
||
</ul>
|
||
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|
||
</div>
|
||
|
||
<!-- MedGen supplemental column ends here -->
|
||
<div class="portlet brieflink">
|
||
<div class="portlet_head">
|
||
<div class="portlet_title">
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<h3>Related information</h3>
|
||
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|
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<div class="portlet_content DiscoveryDbLinks">
|
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<ul>
|
||
<li class="brieflinkpopper">
|
||
<a class="brieflinkpopperctrl" href="/gene?LinkName=medgen_gene_diseases&from_uid=472073" ref="log$=recordlinks">Gene</a>
|
||
<div class="brieflinkpop offscreen_noflow">Related information in NCBI Gene</div>
|
||
</li>
|
||
<li class="brieflinkpopper">
|
||
<a class="brieflinkpopperctrl" href="/gtr/tests?term=CN128903[DISCUI]" ref="log$=recordlinks">GTR</a>
|
||
<div class="brieflinkpop offscreen_noflow">Related information in GTR</div>
|
||
</li>
|
||
<li class="brieflinkpopper">
|
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<a class="brieflinkpopperctrl" href="/gtr/tests?term=CN128903[DISCUI]&test_type=Clinical" ref="log$=recordlinks">GTR(Clinical)</a>
|
||
<div class="brieflinkpop offscreen_noflow">Clinical tests in GTR</div>
|
||
</li>
|
||
<li class="brieflinkpopper">
|
||
<a class="brieflinkpopperctrl" href="/omim?LinkName=medgen_omim_gene&from_uid=472073" ref="log$=recordlinks">OMIM(Genes)</a>
|
||
<div class="brieflinkpop offscreen_noflow">OMIM records containing genes associated with phenotypes registered in MedGen</div>
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||
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<li class="brieflinkpopper">
|
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<a class="brieflinkpopperctrl" href="/pmc?LinkName=medgen_pmc&from_uid=472073" ref="log$=recordlinks">PMC Articles</a>
|
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<div class="brieflinkpop offscreen_noflow">Related information in PubMed Central Links</div>
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|
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<a class="brieflinkpopperctrl" href="/pubmed?LinkName=medgen_pubmed&from_uid=472073" ref="log$=recordlinks">PubMed</a>
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<div class="brieflinkpop offscreen_noflow">Related literature resources in PubMed</div>
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|
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<a class="brieflinkpopperctrl" href="/pubmed?LinkName=medgen_pubmed_bookshelf_cited&from_uid=472073" ref="log$=recordlinks">PubMed (Bookshelf cited)</a>
|
||
<div class="brieflinkpop offscreen_noflow">Links to PubMed based on citations in GeneReviews and Medical Genetics Summaries</div>
|
||
</li>
|
||
</ul>
|
||
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|
||
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|
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<a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=1" href="/portal/utils/pageresolver.fcgi?recordid=67d53a3784f3725e59b9bda5">Simvastatin response</a>
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