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match">◀</a><button id="jr-fip-matches">no matches yet</button><a id="jr-fip-next" class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK425391_"><span class="title" itemprop="name">Propafenone Therapy and <i>CYP2D6</i> Genotype</span></h1><p class="contribs">Dean L.</p><p class="fm-aai"><a href="#_NBK425391_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 10 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="propafenone.Introduction" itemprop="description"><h2 id="_propafenone_Introduction_">Introduction</h2><p>Propafenone is an antiarrhythmic medication. It is used to prevent the reoccurrence of atrial fibrillation in patients with episodic atrial fibrillation who do not have underlying structural heart disease (propafenone may provoke proarrhythmic events in patients with structural heart disease).</p><p>Propafenone belongs to class IC of antiarrhythmic agents and acts on cardiac sodium channels to inhibit action potentials. In general, because of the lack of evidence that antiarrhythmic agents improve survival, they should only be used to treat arrhythmias that are thought to be life-threatening.</p><p>Propafenone is metabolized by CYP2D6, CYP3A4, and CYP1A2 enzymes. Approximately 6% of Caucasians in the US lack CYP2D6 activity, and are known as “CYP2D6 poor metabolizers” (<a href="/books/NBK425391/table/propafenone.T.activity_status_of_selecte/?report=objectonly" target="object" rid-ob="figobpropafenoneTactivitystatusofselecte">Table 1</a>) (<a class="bibr" href="#propafenone.REF.1" rid="propafenone.REF.1">1</a>). Standard doses of propafenone will lead to higher plasma drug concentrations in poor metabolizers, compared to normal metabolizers. In addition, drugs that inhibit CYP2D6, CYP3A4, and CYP1A2 may also increase propafenone levels, which may lead to cardiac arrhythmia episodes.</p><p>The FDA-approved drug label for propafenone states that the recommended dosing regimen of propafenone is the same for all patients (CYP2D6 poor metabolizers and normal metabolizers). However, the label also cautions that the simultaneous use of propafenone with both a CYP2D6 inhibitor (or in patients with CYP2D6 deficiency) and a CYP3A4 inhibitor should be avoided, because of the increased risk of causing arrhythmias and other adverse events (<a class="bibr" href="#propafenone.REF.1" rid="propafenone.REF.1">1</a>).</p><p>A guideline from The Dutch Pharmacogenetics Working Group (DPWG) of the Royal Dutch Pharmacists Association (KNMP) provides dosing recommendations for propafenone, based on <i>CYP2D6</i> genotype. For CYP2D6 poor metabolizers, the guideline recommends reducing the initial dose of propafenone by 70%, ECG monitoring, and monitoring plasma concentrations. For intermediate and ultrarapid metabolizers, the guideline states there is insufficient data to allow for a calculation of dose adjustment. Therefore, it is recommended to adjust the dose in response to plasma concentration and to monitor with ECG, or select an alternative drug (e.g., sotalol, disopyramide, quinidine, amiodarone) (<a class="bibr" href="#propafenone.REF.2" rid="propafenone.REF.2">2</a>, <a class="bibr" href="#propafenone.REF.3" rid="propafenone.REF.3">3</a>) (<a href="/books/NBK425391/table/propafenone.T.cyp2d6_phenotypes_and_the/?report=objectonly" target="object" rid-ob="figobpropafenoneTcyp2d6phenotypesandthe">Table 2</a>).</p></div><div id="propafenone.Drug_class_Antiarrhythmics"><h2 id="_propafenone_Drug_class_Antiarrhythmics_">Drug class: Antiarrhythmics</h2><p>Antiarrhythmic agents suppress abnormal heart rhythms (cardiac arrhythmias), which can originate from the atria (e.g., atrial fibrillation, atrial flutter) or the ventricles (e.g., ventricular tachycardia, ventricular fibrillation).</p><p>There are five main classes of antiarrhythmic agents, based on their primary site of action:</p><ul><li class="half_rhythm"><div>Class I: block sodium (Na+) channels e.g., quinidine (class IA), lidocaine (class IB), propafenone (class IC)</div></li><li class="half_rhythm"><div>Class II: block beta adrenoreceptors e.g., carvedilol, metoprolol, propranolol</div></li><li class="half_rhythm"><div>Class III: block potassium (K+) channels e.g., amiodarone, sotalol</div></li><li class="half_rhythm"><div>Class IV: block calcium (Ca2+) channels e.g., verapamil, diltiazem</div></li><li class="half_rhythm"><div>Class V: work by other or unknown mechanisms e.g., adenosine, digoxin</div></li></ul></div><div id="propafenone.Drug_Propafenone"><h2 id="_propafenone_Drug_Propafenone_">Drug: Propafenone</h2><p>Propafenone is an antiarrhythmic used to prevent the recurrence of atrial fibrillation in patients who have episodic atrial fibrillation and no underlying structural heart disease. Propafenone is also used in the management of paroxysmal supraventricular tachycardia and atrial flutter (<a class="bibr" href="#propafenone.REF.1" rid="propafenone.REF.1">1</a>).</p><p>Because there are no well-controlled studies in pregnant women, the FDA-approved drug label states that propafenone should only be used during pregnancy if the benefit justifies the potential risk to the fetus. The label also states that the safety and effectiveness of propafenone in pediatric patients have not been established.</p><p>Atrial fibrillation is the most common type of harmful cardiac arrhythmias. It is more common in men than women, and the risk of developing atrial fibrillation increases with age. Atrial fibrillation may be paroxysmal (intermittent), persistent (persists for at least 7 days), long-standing (more than 12 months), or permanent.</p><p>The symptoms of atrial fibrillation range from no symptoms, to feeling dizzy, short of breath, and experiencing palpitations. The pulse feels irregular, and an ECG will show an absence of P waves and an irregular QRS complex. Atrial fibrillation can lead to reduced cardiac output, increase the risk of thrombosis and stroke, and affected patients may be at an increased risk for mortality (<a class="bibr" href="#propafenone.REF.4" rid="propafenone.REF.4">4</a>). Management typically includes antithrombotic therapy and rhythm control.</p><p>Propafenone is a class IC <i>antiarrhythmic</i> agent. All class I agents have a "membrane stabilizing effect"—by reducing the fast influx of sodium ions into the cardiac muscle cells, they inhibit the propagation of action potentials. Propafenone also has some Class II activity—it can act as a beta blocker. Side effects of this action include bradycardia and bronchospasm (<a class="bibr" href="#propafenone.REF.5" rid="propafenone.REF.5">5</a>, <a class="bibr" href="#propafenone.REF.6" rid="propafenone.REF.6">6</a>).</p><p>The class IC agents encainide and flecainide have been associated with increasing the risk of cardiac arrest or death, compared to placebo. Consequently all class IC agents, including propafenone, are considered to have a significant risk of provoking proarrhythmic events in patients with structural heart disease. Therefore, propafenone should not be used in patients with underlying structural heart disease. Its use is contraindicated in a number of conditions, including heart failure, conduction disorders, bradycardia, and recent myocardial infarction (within the last 3 months) (<a class="bibr" href="#propafenone.REF.1" rid="propafenone.REF.1">1</a>, <a class="bibr" href="#propafenone.REF.7" rid="propafenone.REF.7">7</a>, <a class="bibr" href="#propafenone.REF.8" rid="propafenone.REF.8">8</a>, <a class="bibr" href="#propafenone.REF.9" rid="propafenone.REF.9">9</a>).</p><p>Propafenone is metabolized into two active metabolites: 5-hydroxypropafenone, which is formed by CYP2D6, and norpropafenone, which is formed by both CYP3A4 and CYP1A2. Multiple studies have found that genetic variants in the <i>CYP2D6</i> gene influence the plasma drug levels of propafenone (<a class="bibr" href="#propafenone.REF.10" rid="propafenone.REF.10">10</a>, <a class="bibr" href="#propafenone.REF.11" rid="propafenone.REF.11">11</a>, <a class="bibr" href="#propafenone.REF.12" rid="propafenone.REF.12">12</a>, <a class="bibr" href="#propafenone.REF.13" rid="propafenone.REF.13">13</a>).</p><p>In patients who lack CYP2D6 activity, metabolism of propafenone is slower, so the 5-hydroxy metabolite is not formed or is formed at very slow rates. In these patients, high doses of propafenone (850mg daily) lead to plasma concentrations of propafenone that are about twice those of patients who have normal CYP2D6 activity. At lower initial doses, the difference between propafenone and 5-hydroxy metabolite concentrations is even greater (<a class="bibr" href="#propafenone.REF.1" rid="propafenone.REF.1">1</a>, <a class="bibr" href="#propafenone.REF.14" rid="propafenone.REF.14">14</a>).</p><p>However, the FDA recommends that the dosing regimen of propafenone should be the same for all patients, regardless of their CYP2D6 activity levels. This is because even at high doses, the effects of high propafenone levels are mitigated by the lack of the active 5-hydroxy metabolite in the slow metabolizers, and also because steady-state conditions are achieved after 4 to 5 days of titrating the dose in all patients. But the FDA also recommends that because of the large variation in plasma drug levels between individuals, the dose of propafenone should be individually titrated on the basis of response and tolerance, with close attention paid to clinical and ECG evidence of toxicity (<a class="bibr" href="#propafenone.REF.1" rid="propafenone.REF.1">1</a>).</p><p>The FDA-approved drug label for propafenone cautions against the simultaneous use of propafenone with both a CYP2D6 inhibitor and a CYP3A4 inhibitor. This is because the combination of CYP3A4 inhibition and either CYP2D6 inhibition or deficiency may increase propafenone exposure, which may trigger new cardiac arrhythmias and exaggerate beta adrenoreceptor blockage (<a class="bibr" href="#propafenone.REF.1" rid="propafenone.REF.1">1</a>).</p></div><div id="propafenone.The_Cytochrome_P450_Superfam"><h2 id="_propafenone_The_Cytochrome_P450_Superfam_">The Cytochrome P450 Superfamily</h2><p>The cytochrome P450 superfamily (CYP450) is a large and diverse group of enzymes that form the major system for metabolizing lipids, hormones, toxins, and drugs. The <i>CYP450</i> genes are very polymorphic and can result in reduced, absent, or increased enzyme activity.</p></div><div id="propafenone.Gene_CYP2D6"><h2 id="_propafenone_Gene_CYP2D6_">Gene: <i>CYP2D6</i></h2><p><i>CYP2D6</i> is highly polymorphic, with over 100 star (*) alleles described (<a class="bibr" href="#propafenone.REF.15" rid="propafenone.REF.15">15</a>). <i>CYP2D6*1</i> is the reference (or wild-type) allele encoding enzyme with normal activity. The <i>CYP2D6*2</i>, *<i>33</i>, and <i>*35</i> alleles are also considered to confer normal activity (<a href="/books/NBK425391/table/propafenone.T.activity_status_of_selecte/?report=objectonly" target="object" rid-ob="figobpropafenoneTactivitystatusofselecte">Table 1</a>).</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figpropafenoneTactivitystatusofselecte"><a href="/books/NBK425391/table/propafenone.T.activity_status_of_selecte/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobpropafenoneTactivitystatusofselecte"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="propafenone.T.activity_status_of_selecte"><a href="/books/NBK425391/table/propafenone.T.activity_status_of_selecte/?report=objectonly" target="object" rid-ob="figobpropafenoneTactivitystatusofselecte">Table 1. </a></h4><p class="float-caption no_bottom_margin">Activity status of selected <i>CYP2D6</i> alleles </p></div></div><p>Individuals who have more than two normal function copies of the <i>CYP2D6</i> (<i>CYP2D6*xN</i>) gene are “ultrarapid metabolizers,” whereas individuals who carry two normal or one normal and one decreased function allele are classified as “normal metabolizers.”</p><p>Individuals with one normal and one no function allele or two decreased function alleles are categorized as “normal metabolizers” by recent nomenclature guidelines (<a class="bibr" href="#propafenone.REF.16" rid="propafenone.REF.16">16</a>), but have also been categorized as “intermediate metabolizers” in the literature. Subjects with one decreased and one no function allele are predicted to be intermediate metabolizers and those with two no function alleles are classified as poor metabolizers.</p><p>The most common no function alleles include <i>CYP2D6*3</i>, <i>*4</i>, <i>*5</i>, and <i>*6</i> (<a class="bibr" href="#propafenone.REF.17" rid="propafenone.REF.17">17</a>, <a class="bibr" href="#propafenone.REF.18" rid="propafenone.REF.18">18</a>, <a class="bibr" href="#propafenone.REF.19" rid="propafenone.REF.19">19</a>, <a class="bibr" href="#propafenone.REF.20" rid="propafenone.REF.20">20</a>), and the most common decreased function alleles include <i>CYP2D6*9, *10, *17, *29</i> and <i>*41</i> (<a class="bibr" href="#propafenone.REF.5" rid="propafenone.REF.5">5</a>, <a class="bibr" href="#propafenone.REF.6" rid="propafenone.REF.6">6</a>, <a class="bibr" href="#propafenone.REF.18" rid="propafenone.REF.18">18</a>, <a class="bibr" href="#propafenone.REF.20" rid="propafenone.REF.20">20</a>, <a class="bibr" href="#propafenone.REF.21" rid="propafenone.REF.21">21</a>) (<a href="/books/NBK425391/table/propafenone.T.activity_status_of_selecte/?report=objectonly" target="object" rid-ob="figobpropafenoneTactivitystatusofselecte">Table 1</a>).</p><p>There are large inter-ethnic differences in the frequency of these alleles. For example, <i>CYP2D6*4</i> is the most common no function allele in Caucasians, but is less abundant in subjects with African ancestry, and is rare in Asians. In contrast, the decreased function allele <i>CYP2D6*10</i> is the most common allele in Asians, and <i>CYP2D6</i>*<i>17</i> is almost exclusively found in individuals with African ancestry (<a class="bibr" href="#propafenone.REF.22" rid="propafenone.REF.22">22</a>).</p><p>Consequently, the phenotype frequencies vary substantially among the major ethnicities and may vary among populations. Approximately 6-10% of European Caucasians and their descendants are poor metabolizers, mainly due to the prevalent no function <i>CYP2D6*4</i> and <i>*5</i> alleles (<a class="bibr" href="#propafenone.REF.17" rid="propafenone.REF.17">17</a>, <a class="bibr" href="#propafenone.REF.23" rid="propafenone.REF.23">23</a>).</p></div><div id="propafenone.Genetic_Testing"><h2 id="_propafenone_Genetic_Testing_">Genetic Testing</h2><p>The NIH’s Genetic Testing Registry (GTR) lists genetic tests currently available for <a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=CN078001" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">propafenone response</a> and the <a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=1565%5Bgeneid%5D" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CYP2D6 gene</a>.</p><p>Results are typically reported as a diplotype, such as <i>CYP2D6 *1/*1</i> (wild type). A result for copy number, if available, is also important when interpreting <i>CYP2D6</i> results (<a class="bibr" href="#propafenone.REF.19" rid="propafenone.REF.19">19</a>).</p></div><div id="propafenone.Therapeutic_Recommendations"><h2 id="_propafenone_Therapeutic_Recommendations_">Therapeutic Recommendations based on Genotype</h2><p><b>This section contains excerpted</b><sup><a href="#propafenone.FN1">1</a></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>2016 Statement from the US Food and Drug Administration (FDA):</b> Propafenone is metabolized by CYP2D6, CYP3A4, and CYP1A2 isoenzymes. Approximately 6% of Caucasians in the US population are naturally deficient in CYP2D6 activity and other demographic groups are deficient to a somewhat lesser extent. Drugs that inhibit these CYP pathways (such as desipramine, paroxetine, ritonavir, sertraline for CYP2D6; ketoconazole, erythromycin, saquinavir, and grapefruit juice for CYP3A4; and amiodarone and tobacco smoke for CYP1A2) can be expected to cause increased plasma levels of propafenone.</p><p>Increased exposure to propafenone may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity. Because of its metabolism, the combination of CYP3A4 inhibition and either CYP2D6 deficiency or CYP2D6 inhibition in users of propafenone is potentially hazardous. Therefore, avoid simultaneous use of propafenone with both a CYP2D6 inhibitor and a CYP3A4 inhibitor.</p><p><b>Please review the complete therapeutic recommendations that are located here:</b> (<a class="bibr" href="#propafenone.REF.1" rid="propafenone.REF.1">1</a>).</p><p><b>2016 Summary of recommendations from The Dutch Pharmacogenetics Working Group (DPWG) of the Royal Dutch Pharmacists Association (KNMP):</b> For CYP2D6 poor metabolizers (PMs), defined as patients carrying two defective alleles, dose reductions are recommended for clomipramine, flecainide, haloperidol, zuclopenthixol (all 50%); doxepin, nortriptyline (both 60%); imipramine, propafenone (both 70%); and metoprolol (75%).</p><p>[…].</p><p>For CYP2D6 intermediate metabolizers (IMs), defined as patients carrying two decreased-activity alleles or one active/decreased-activity allele and one inactive allele, dose reductions ranging from 20 to 50% are advised for doxepin, amitriptyline, zuclopenthixol, imipramine, nortriptyline, and metoprolol. There were insufficient data to calculate dose adjustments for clomipramine, oxycodone, propafenone, risperidone, and venlafaxine (Table 2).</p><p><b>Please review the complete therapeutic recommendations that are located here:</b> (<a class="bibr" href="#propafenone.REF.2" rid="propafenone.REF.2">2</a>, <a class="bibr" href="#propafenone.REF.3" rid="propafenone.REF.3">3</a>).</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figpropafenoneTcyp2d6phenotypesandthe"><a href="/books/NBK425391/table/propafenone.T.cyp2d6_phenotypes_and_the/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobpropafenoneTcyp2d6phenotypesandthe"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="propafenone.T.cyp2d6_phenotypes_and_the"><a href="/books/NBK425391/table/propafenone.T.cyp2d6_phenotypes_and_the/?report=objectonly" target="object" rid-ob="figobpropafenoneTcyp2d6phenotypesandthe">Table 2. </a></h4><p class="float-caption no_bottom_margin"><i>CYP2D6</i> phenotypes and the therapeutic recommendations for propafenone therapy, from The Dutch Pharmacogenetics Working Group (2016) </p></div></div></div><div id="propafenone.Nomenclature_of_selected_CYP"><h2 id="_propafenone_Nomenclature_of_selected_CYP_">Nomenclature of selected <i>CYP2D6</i> alleles</h2><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figpropafenoneTe"><a href="/books/NBK425391/table/propafenone.Te/?report=objectonly" target="object" title="Table" class="img_link icnblk_img" rid-ob="figobpropafenoneTe"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="propafenone.Te"><a href="/books/NBK425391/table/propafenone.Te/?report=objectonly" target="object" rid-ob="figobpropafenoneTe">Table</a></h4></div></div><p>Guidelines for the description and nomenclature of gene variations are available from the Human Genome Variation Society (HGVS) (<a class="bibr" href="#propafenone.REF.24" rid="propafenone.REF.24">24</a>)</p><p>Nomenclature for Cytochrome P450 enzymes is available from the Pharmacogene Variation Consortium (PharmVar) <a href="https://www.pharmvar.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://www.pharmvar.org/</a>.</p></div><div id="propafenone.Acknowledgments"><h2 id="_propafenone_Acknowledgments_">Acknowledgments</h2><p>The author would like to thank the following individuals for reviewing this summary: JT Callaghan, M.D., Ph.D., Associate Dean of Veterans Affairs Research, Associate Professor of Medicine, and Pharmacology and Toxicology, Department of Veterans Affairs, and Indiana University School of Medicine; Ben Kong, PharmD, BCPS, Clinical Pharmacist, Oregon Health & Science University, Oregon; Gouri Mukerjee, Scientific Officer at Geneyouin Inc., Toronto, Canada; Mohamed Nagy, Clinical Pharmacist, Head of the Personalised Medication Management Unit, Department of Pharmaceutical Services, Children's Cancer Hospital, Egypt; Mandy van Rhenen, Secretary of the Dutch Pharmacogenetics Working Group (DPWG), Centre for Information on Medicines, Royal Dutch Pharmacists Association (KNMP); and DeeAnn Visk, PhD, a medical writer, editor, and member of the Clinical Pharmacogenetics Implementation Consortium (CPIC).</p></div><div id="propafenone.References"><h2 id="_propafenone_References_">References</h2><dl class="temp-labeled-list"><dl class="bkr_refwrap"><dt>1.</dt><dd><div class="bk_ref" id="propafenone.REF.1">RYTHMOL SR- propafenone hydrochloride capsule, extended release [Package insert]. Germany: LLC, G.; 2016. Available from: <a href="https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8bb1bc4a-a019-49c8-af81-be899822428f" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">https://dailymed<wbr style="display:inline-block"></wbr>​.nlm<wbr style="display:inline-block"></wbr>​.nih.gov/dailymed/drugInfo<wbr style="display:inline-block"></wbr>​.cfm?setid=8bb1bc4a-a019-49c8-af81-be899822428f</a>.</div></dd></dl><dl class="bkr_refwrap"><dt>2.</dt><dd><div class="bk_ref" id="propafenone.REF.2">Swen J.J., Nijenhuis M., de Boer A., Grandia L., et al. Pharmacogenetics: from bench to byte--an update of guidelines. <span><span class="ref-journal">Clin Pharmacol Ther. </span>2011;<span class="ref-vol">89</span>(5):662–73.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21412232" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21412232</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>3.</dt><dd><div class="bk_ref" id="propafenone.REF.3">Kalman L.V., Agundez J., Appell M.L., Black J.L., et al. Pharmacogenetic allele nomenclature: International workgroup recommendations for test result reporting. <span><span class="ref-journal">Clin Pharmacol Ther. </span>2016;<span class="ref-vol">99</span>(2):172–85.</span> [<a href="/pmc/articles/PMC4724253/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4724253</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26479518" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26479518</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>4.</dt><dd><div class="bk_ref" id="propafenone.REF.4">Andersson T., Magnuson A., Bryngelsson I.L., Frobert O., et al. All-cause mortality in 272,186 patients hospitalized with incident atrial fibrillation 1995-2008: a Swedish nationwide long-term case-control study. <span><span class="ref-journal">Eur Heart J. </span>2013;<span class="ref-vol">34</span>(14):1061–7.</span> [<a href="/pmc/articles/PMC3618889/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3618889</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23321349" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23321349</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>5.</dt><dd><div class="bk_ref" id="propafenone.REF.5">Stoschitzky K., Stoschitzky G., Lercher P., Brussee H., et al. Propafenone shows class Ic and class II antiarrhythmic effects. <span><span class="ref-journal">Europace. </span>2016;<span class="ref-vol">18</span>(4):568–71.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/26056191" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26056191</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>6.</dt><dd><div class="bk_ref" id="propafenone.REF.6">Darbar D., Roden D.M. Pharmacogenetics of antiarrhythmic therapy. <span><span class="ref-journal">Expert Opin Pharmacother. </span>2006;<span class="ref-vol">7</span>(12):1583–90.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16872261" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16872261</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>7.</dt><dd><div class="bk_ref" id="propafenone.REF.7">Echt D.S., Liebson P.R., Mitchell L.B., Peters R.W., et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. <span><span class="ref-journal">N Engl J Med. </span>1991;<span class="ref-vol">324</span>(12):781–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/1900101" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1900101</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>8.</dt><dd><div class="bk_ref" id="propafenone.REF.8">Vaughan Williams E.M. Significance of classifying antiarrhythmic actions since the cardiac arrhythmia suppression trial. <span><span class="ref-journal">J Clin Pharmacol. </span>1991;<span class="ref-vol">31</span>(2):123–35.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/1901320" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1901320</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>9.</dt><dd><div class="bk_ref" id="propafenone.REF.9">Lin C.Y., Lin Y.J., Lo L.W., Chen Y.Y., et al. Factors predisposing to ventricular proarrhythmia during antiarrhythmic drug therapy for atrial fibrillation in patients with structurally normal heart. <span><span class="ref-journal">Heart Rhythm. </span>2015;<span class="ref-vol">12</span>(7):1490–500.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/25889809" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25889809</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>10.</dt><dd><div class="bk_ref" id="propafenone.REF.10">Cai W.M., Xu J., Chen B., Zhang F.M., et al. Effect of CYP2D6*10 genotype on propafenone pharmacodynamics in Chinese patients with ventricular arrhythmia. <span><span class="ref-journal">Acta Pharmacol Sin. </span>2002;<span class="ref-vol">23</span>(11):1040–4.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12421483" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12421483</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>11.</dt><dd><div class="bk_ref" id="propafenone.REF.11">Chen B., Cai W.M. Influence of CYP2D6*10B genotype on pharmacokinetics of propafenone enantiomers in Chinese subjects. <span><span class="ref-journal">Acta Pharmacol Sin. </span>2003;<span class="ref-vol">24</span>(12):1277–80.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/14653957" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14653957</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>12.</dt><dd><div class="bk_ref" id="propafenone.REF.12">Zhou S.F. Polymorphism of human cytochrome P450 2D6 and its clinical significance: Part I. <span><span class="ref-journal">Clin Pharmacokinet. </span>2009;<span class="ref-vol">48</span>(11):689–723.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19817501" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19817501</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>13.</dt><dd><div class="bk_ref" id="propafenone.REF.13">Su Y., Liang B.Q., Feng Y.L., Zhan Y., et al. Assessment of 25 CYP2D6 alleles found in the Chinese population on propafenone metabolism in vitro. <span><span class="ref-journal">Can J Physiol Pharmacol. </span>2016;<span class="ref-vol">94</span>(8):895–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27203132" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27203132</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>14.</dt><dd><div class="bk_ref" id="propafenone.REF.14">Lee J.T., Kroemer H.K., Silberstein D.J., Funck-Brentano C., et al. The role of genetically determined polymorphic drug metabolism in the beta-blockade produced by propafenone. <span><span class="ref-journal">N Engl J Med. </span>1990;<span class="ref-vol">322</span>(25):1764–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/1971708" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1971708</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>15.</dt><dd><div class="bk_ref" id="propafenone.REF.15">The Human Cytochrome P450 (CYP) Allele Nomenclature Database [Internet]. CYP2D6 allele nomenclature [Cited 14 December 2015]. Available from: <a href="https://www.pharmvar.org/" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">https://www<wbr style="display:inline-block"></wbr>​.pharmvar.org/</a></div></dd></dl><dl class="bkr_refwrap"><dt>16.</dt><dd><div class="bk_ref" id="propafenone.REF.16">Caudle K.E., Dunnenberger H.M., Freimuth R.R., Peterson J.F., et al. Standardizing terms for clinical pharmacogenetic test results: consensus terms from the Clinical Pharmacogenetics Implementation Consortium (CPIC). <span><span class="ref-journal">Genet Med. </span>2016</span> [<a href="/pmc/articles/PMC5253119/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5253119</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27441996" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27441996</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>17.</dt><dd><div class="bk_ref" id="propafenone.REF.17">Lerena L.A., Naranjo M.E., Rodrigues-Soares F., Penas L.E.M., et al. Interethnic variability of CYP2D6 alleles and of predicted and measured metabolic phenotypes across world populations. <span><span class="ref-journal">Expert Opin Drug Metab Toxicol. </span>2014;<span class="ref-vol">10</span>(11):1569–83.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/25316321" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25316321</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>18.</dt><dd><div class="bk_ref" id="propafenone.REF.18">PharmGKB [Internet]. Palo Alto (CA): Stanford University. Haplotype CYP2D6*9 [Cited 17 October 2016]. Available from: <a href="https://www.pharmgkb.org/haplotype/PA165948317" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">https://www<wbr style="display:inline-block"></wbr>​.pharmgkb<wbr style="display:inline-block"></wbr>​.org/haplotype/PA165948317</a>.</div></dd></dl><dl class="bkr_refwrap"><dt>19.</dt><dd><div class="bk_ref" id="propafenone.REF.19">Hicks J.K., Bishop J.R., Sangkuhl K., Muller D.J., et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors. <span><span class="ref-journal">Clin Pharmacol Ther. </span>2015;<span class="ref-vol">98</span>(2):127–34.</span> [<a href="/pmc/articles/PMC4512908/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4512908</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25974703" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25974703</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>20.</dt><dd><div class="bk_ref" id="propafenone.REF.20">PharmGKB [Internet]. Palo Alto (CA): Stanford University. Haplotype CYP2D6*29 [Cited 17 October 2016]. Available from: <a href="https://www.pharmgkb.org/haplotype/PA165948318" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">https://www<wbr style="display:inline-block"></wbr>​.pharmgkb<wbr style="display:inline-block"></wbr>​.org/haplotype/PA165948318</a>.</div></dd></dl><dl class="bkr_refwrap"><dt>21.</dt><dd><div class="bk_ref" id="propafenone.REF.21">PharmGKB [Internet]. Palo Alto (CA): Stanford University. Haplotype CYP2D6*41 [Cited 8 October 2015]. Available from: <a href="http://www.pharmgkb.org/haplotype/PA165816584" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">http://www<wbr style="display:inline-block"></wbr>​.pharmgkb.org<wbr style="display:inline-block"></wbr>​/haplotype/PA165816584</a>.</div></dd></dl><dl class="bkr_refwrap"><dt>22.</dt><dd><div class="bk_ref" id="propafenone.REF.22">Gaedigk A., Sangkuhl K., Whirl-Carrillo M., Klein T., et al. Prediction of CYP2D6 phenotype from genotype across world populations. <span><span class="ref-journal">Genet Med. </span>2016</span> [<a href="/pmc/articles/PMC5292679/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5292679</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27388693" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27388693</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>23.</dt><dd><div class="bk_ref" id="propafenone.REF.23">Bradford L.D. CYP2D6 allele frequency in European Caucasians, Asians, Africans and their descendants. <span><span class="ref-journal">Pharmacogenomics. </span>2002;<span class="ref-vol">3</span>(2):229–43.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11972444" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11972444</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>24.</dt><dd><div class="bk_ref" id="propafenone.REF.24">den Dunnen, J.T., R.
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Dalgleish, D.R.
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Maglott, R.K.
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Hart, et al. <span class="ref-title">HGVS Recommendations for the Description of Sequence Variants: 2016 Update. </span><span class="ref-journal">Hum Mutat</span>, 2016.37(6): p.564-9.
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[<a href="https://pubmed.ncbi.nlm.nih.gov/26931183" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26931183</span></a>]</div></dd></dl></dl></div><h2 id="NBK425391_footnotes">Footnotes</h2><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>
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<sup>1</sup>
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</dt><dd><div id="propafenone.FN1"><p class="no_top_margin"> The FDA labels 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.</p></div></dd></dl></dl><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK425391_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><p class="contrib-group"><h4>Authors</h4><span itemprop="author">Laura Dean</span>, MD<sup>1</sup>.</p><h4>Affiliations</h4><div class="affiliation"><sup>1</sup> NCBI<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="vog.hin.mln.ibcn@naed" class="oemail">vog.hin.mln.ibcn@naed</a></div></div><h3>Publication History</h3><p class="small">Created: <span itemprop="datePublished">April 4, 2017</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright Notice</a><p class="small">All Medical Genetics Summaries content, except where otherwise noted, is licensed under a Creative Commons <a href="https://creativecommons.org/licenses/by/4.0/" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=uri">Attribution 4.0 International (CC BY 4.0)</a> license which permits copying, distribution, and adaptation of the work, provided the original work is properly cited and any changes from the original work are properly indicated. Any altered, transformed, or adapted form of the work may only be distributed under the same or similar license to this one.</p></div></div><h3>Publisher</h3><p><a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=books" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">National Center for Biotechnology Information (US)</a>, Bethesda (MD)</p><h3>NLM Citation</h3><p>Dean L. Propafenone Therapy and CYP2D6 Genotype. 2017 Apr 4. In: Pratt VM, Scott SA, Pirmohamed M, et al., editors. Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2012-. <span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/gtrbook/primaquine/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/gtrbook/rasburicase/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="table-wrap" id="figobpropafenoneTactivitystatusofselecte"><div id="propafenone.T.activity_status_of_selecte" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Activity status of selected <i>CYP2D6</i> alleles</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK425391/table/propafenone.T.activity_status_of_selecte/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__propafenone.T.activity_status_of_selecte_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_propafenone.T.activity_status_of_selecte_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Allele type</th><th id="hd_h_propafenone.T.activity_status_of_selecte_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><i>CYP2D6</i> Alleles</th></tr></thead><tbody><tr><td headers="hd_h_propafenone.T.activity_status_of_selecte_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Normal function</td><td headers="hd_h_propafenone.T.activity_status_of_selecte_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<i>*1, *2, *33, *35</i>
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</td></tr><tr><td headers="hd_h_propafenone.T.activity_status_of_selecte_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Decreased function</td><td headers="hd_h_propafenone.T.activity_status_of_selecte_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<i>*9, *10, *17, *29, *36, *41</i>
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</td></tr><tr><td headers="hd_h_propafenone.T.activity_status_of_selecte_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No function</td><td headers="hd_h_propafenone.T.activity_status_of_selecte_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<i>*3-*8, *11-*16, *19-*21, *38, *40, *42</i>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">For a detailed list of <i>CYP2D6</i> alleles, please see (<a class="bibr" href="#propafenone.REF.15" rid="propafenone.REF.15">15</a>).</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobpropafenoneTcyp2d6phenotypesandthe"><div id="propafenone.T.cyp2d6_phenotypes_and_the" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p><i>CYP2D6</i> phenotypes and the therapeutic recommendations for propafenone therapy, from The Dutch Pharmacogenetics Working Group (2016)</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK425391/table/propafenone.T.cyp2d6_phenotypes_and_the/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__propafenone.T.cyp2d6_phenotypes_and_the_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_propafenone.T.cyp2d6_phenotypes_and_the_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CYP2D6 Phenotype</th><th id="hd_h_propafenone.T.cyp2d6_phenotypes_and_the_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Recommendations for propafenone therapy</th></tr></thead><tbody><tr><td headers="hd_h_propafenone.T.cyp2d6_phenotypes_and_the_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ultrarapid metabolizer</td><td headers="hd_h_propafenone.T.cyp2d6_phenotypes_and_the_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Insufficient data to allow calculation of dose adjustment. Adjust dose in response to plasma concentration and record ECG or select alternative drug (e.g., sotalol, disopyramide, quinidine, amiodarone).</td></tr><tr><td headers="hd_h_propafenone.T.cyp2d6_phenotypes_and_the_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Intermediate metabolizer</td><td headers="hd_h_propafenone.T.cyp2d6_phenotypes_and_the_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Insufficient data to allow calculation of dose adjustment. Adjust dose in response to plasma concentration and record ECG or select alternative drug (e.g., sotalol, disopyramide, quinidine, amiodarone).</td></tr><tr><td headers="hd_h_propafenone.T.cyp2d6_phenotypes_and_the_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Poor metabolizer</td><td headers="hd_h_propafenone.T.cyp2d6_phenotypes_and_the_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Reduce dose by 70%, record ECG, monitor plasma concentration</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">The level of evidence for the therapeutic (dose) recommendations is 4/4 (“good quality”) for poor metabolizers, and 3/4 (“moderate quality”) for intermediate and ultrarapid metabolizer types. The Table is adapted from Swen J.J., Nijenhuis M., de Boer A., Grandia L. et al. Pharmacogenetics: from bench to byte - an update of guidelines. Clinical pharmacology and therapeutics. 2011;89(<a class="bibr" href="#propafenone.REF.5" rid="propafenone.REF.5">5</a>):662–73 (<a class="bibr" href="#propafenone.REF.2" rid="propafenone.REF.2">2</a>, <a class="bibr" href="#propafenone.REF.3" rid="propafenone.REF.3">3</a>).</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobpropafenoneTe"><div id="propafenone.Te" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK425391/table/propafenone.Te/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__propafenone.Te_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_propafenone.Te_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_propafenone.Te_1_1_1_1" style="text-align:left;vertical-align:top;">Common allele name</th><th id="hd_h_propafenone.Te_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_propafenone.Te_1_1_1_2" style="text-align:left;vertical-align:top;">Alternative names</th><th id="hd_h_propafenone.Te_1_1_1_3" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:top;">HGVS reference sequence</th><th id="hd_h_propafenone.Te_1_1_1_4" rowspan="2" scope="col" colspan="1" headers="hd_h_propafenone.Te_1_1_1_4" style="text-align:left;vertical-align:top;">dbSNP reference identifier for allele location</th></tr><tr><th headers="hd_h_propafenone.Te_1_1_1_3" id="hd_h_propafenone.Te_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:top;">Coding</th><th headers="hd_h_propafenone.Te_1_1_1_3" id="hd_h_propafenone.Te_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Protein</th></tr></thead><tbody><tr><td headers="hd_h_propafenone.Te_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<i>CYP2D6*4</i>
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</td><td headers="hd_h_propafenone.Te_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1846G>A</td><td headers="hd_h_propafenone.Te_1_1_1_3 hd_h_propafenone.Te_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/clinvar/variation/16889/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000106.5:c.506-1G>A</a>
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</td><td headers="hd_h_propafenone.Te_1_1_1_3 hd_h_propafenone.Te_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Variant occurs in a non-coding region (splice variant causes a frameshift)</td><td headers="hd_h_propafenone.Te_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="https://www.ncbi.nlm.nih.gov/snp/rs3892097" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">rs3892097</a>
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</td></tr><tr><td headers="hd_h_propafenone.Te_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<i>CYP2D6*5</i>
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</td><td headers="hd_h_propafenone.Te_1_1_1_2 hd_h_propafenone.Te_1_1_1_3 hd_h_propafenone.Te_1_1_2_1 hd_h_propafenone.Te_1_1_2_2 hd_h_propafenone.Te_1_1_1_4" colspan="4" rowspan="1" style="text-align:left;vertical-align:top;">Variant results in a whole gene deletion</td></tr><tr><td headers="hd_h_propafenone.Te_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<i>CYP2D6*6</i>
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</td><td headers="hd_h_propafenone.Te_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1707 del T Trp152Gly<br />CYP2D6T</td><td headers="hd_h_propafenone.Te_1_1_1_3 hd_h_propafenone.Te_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/clinvar/variation/16891/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000106.5:c.454delT</a>
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</td><td headers="hd_h_propafenone.Te_1_1_1_3 hd_h_propafenone.Te_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/clinvar/variation/16891/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000097.3:p.Trp152Glyfs</a>
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</td><td headers="hd_h_propafenone.Te_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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|
<a href="https://www.ncbi.nlm.nih.gov/snp/rs5030655" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">rs5030655</a>
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|
</td></tr><tr><td headers="hd_h_propafenone.Te_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<i>CYP2D6*10</i>
|
|
</td><td headers="hd_h_propafenone.Te_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">100C>T (Pro34Ser)</td><td headers="hd_h_propafenone.Te_1_1_1_3 hd_h_propafenone.Te_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/clinvar/variation/16893/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000106.5:c.100C>T</a>
|
|
</td><td headers="hd_h_propafenone.Te_1_1_1_3 hd_h_propafenone.Te_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/clinvar/variation/16893/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000097.3:p.Pro34Ser</a>
|
|
</td><td headers="hd_h_propafenone.Te_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/snp/rs1065852" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">rs1065852</a>
|
|
</td></tr><tr><td headers="hd_h_propafenone.Te_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<i>CYP2D6*17</i>
|
|
</td><td headers="hd_h_propafenone.Te_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1023C>T<sup>[1]</sup> (Thr107Ile)</td><td headers="hd_h_propafenone.Te_1_1_1_3 hd_h_propafenone.Te_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="/nuccore/392513720" class="bk_tag" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=nuccore">NM_000106.5</a>:c.320C>T</td><td headers="hd_h_propafenone.Te_1_1_1_3 hd_h_propafenone.Te_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="/protein/392513721/?report=GenPept" class="bk_tag" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=genpept">NP_000097.3</a>:p.Thr107Ile</td><td headers="hd_h_propafenone.Te_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/snp/rs28371706" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">rs28371706</a>
|
|
</td></tr><tr><td headers="hd_h_propafenone.Te_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:top;">2850C>T<sup>[2]</sup> (Cys296Arg)</td><td headers="hd_h_propafenone.Te_1_1_1_3 hd_h_propafenone.Te_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/clinvar/variation/16895/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000106.5:c.886T>C</a>
|
|
</td><td headers="hd_h_propafenone.Te_1_1_1_3 hd_h_propafenone.Te_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/clinvar/variation/16895/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000097.3:p.Cys296Arg</a>
|
|
</td><td headers="hd_h_propafenone.Te_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/snp/rs16947" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">rs16947</a>
|
|
</td></tr><tr><td headers="hd_h_propafenone.Te_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<i>CYP2D6*41</i>
|
|
</td><td headers="hd_h_propafenone.Te_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2850C>T<sup>[2]</sup><br />(Cys296Arg)</td><td headers="hd_h_propafenone.Te_1_1_1_3 hd_h_propafenone.Te_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/clinvar/variation/16895/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000106.5:c.886T>C</a>
|
|
</td><td headers="hd_h_propafenone.Te_1_1_1_3 hd_h_propafenone.Te_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/clinvar/variation/16895/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000097.3:p.Cys296Arg</a>
|
|
</td><td headers="hd_h_propafenone.Te_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/snp/rs16947" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">rs16947</a>
|
|
</td></tr><tr><td headers="hd_h_propafenone.Te_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:top;">2988G>A</td><td headers="hd_h_propafenone.Te_1_1_1_3 hd_h_propafenone.Te_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="/nuccore/392513720" class="bk_tag" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=nuccore">NM_000106.5</a>:c.985+39G>A</td><td headers="hd_h_propafenone.Te_1_1_1_3 hd_h_propafenone.Te_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Variant occurs in a non-coding region (impacts slicing).</td><td headers="hd_h_propafenone.Te_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/snp/rs28371725" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">rs28371725</a>
|
|
</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>
|
|
<sup>[1]</sup>
|
|
</dt><dd><div id="propafenone.TF.e.1"><p class="no_margin">In the literature, 1023C>T is also referred to as 1111C>T, and 2850C>T is also referred to 2938C>T.</p></div></dd></dl><dl class="bkr_refwrap"><dt>
|
|
<sup>[2]</sup>
|
|
</dt><dd><div id="propafenone.TF.e.2"><p class="no_margin">In the literature, 2850C>T is also referred to as 2938C>T.</p></div></dd></dl></dl></div></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script><script type="text/javascript">if (typeof (jQuery) != 'undefined') { (function ($) { $(function () { var min = Math.ceil(1); var max = Math.floor(100000); var randomNum = Math.floor(Math.random() * (max - min)) + min; var surveyUrl = "/projects/Gene/portal/surveys/seqdbui-survey.js?rando=" + randomNum.toString(); $.getScript(surveyUrl, function () { try { ncbi.seqDbUISurvey.init(); } catch (err) { console.info(err); } }).fail(function (jqxhr, settings, exception) { console.info('Cannot load survey script', jqxhr); });; }); })(jQuery); };</script></div></div>
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