Association Between CYP2C9 Genetic Variants and Anticoagulation-Related Outcomes During Warfarin Therapy
CONTEXT Warfarin is a commonly used anticoagulant that requires careful clinical management to balance the risks of overanticoagulation and bleeding with those of underanticoagulation and clotting. The principal enzyme involved in warfarin metabolism is CYP2C9, and 2 relatively common variant forms...
Gespeichert in:
| Veröffentlicht in: | JAMA : the journal of the American Medical Association 2002-04, Vol.287 (13), p.1690-1698 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1698 |
|---|---|
| container_issue | 13 |
| container_start_page | 1690 |
| container_title | JAMA : the journal of the American Medical Association |
| container_volume | 287 |
| creator | Higashi, Mitchell K Veenstra, David L Kondo, L. Midori Wittkowsky, Ann K Srinouanprachanh, Sengkeo L Farin, Fred M Rettie, Allan E |
| description | CONTEXT Warfarin is a commonly used anticoagulant that requires careful clinical
management to balance the risks of overanticoagulation and bleeding with those
of underanticoagulation and clotting. The principal enzyme involved in warfarin
metabolism is CYP2C9, and 2 relatively common variant forms with reduced activity
have been identified, CYP2C9*2 and CYP2C9*3. Patients with these genetic variants have been shown to require
lower maintenance doses of warfarin, but a direct association between CYP2C9
genotype and anticoagulation status or bleeding risk has not been established. OBJECTIVE To determine if CYP2C9*2 and CYP2C9*3 variants are associated with overanticoagulation and bleeding
events during warfarin therapy. DESIGN AND SETTING Retrospective cohort study conducted at 2 anticoagulation clinics based
in Seattle, Wash. PARTICIPANTS Two hundred patients receiving long-term warfarin therapy for various
indications during April 3, 1990, to May 31, 2001. Only patients with a complete
history of warfarin exposure were included. MAIN OUTCOME MEASURES Anticoagulation status, measured by time to therapeutic international
normalized ratio (INR), rate of above-range INRs, and time to stable warfarin
dosing; and time to serious or life-threatening bleeding events. RESULTS Among 185 patients with analyzable data, 58 (31.4%) had at least 1 variant
CYP2C9 allele and 127 (68.6%) had the wild-type (*1/*1)
genotype. Mean maintenance dose varied significantly among the 6 genotype
groups (*1/*1 [n = 127], *1/*2 [n = 28], *1/*3 [n = 18], *2/*2 [n = 4], *2/*3 [n = 3], *3/*3 [n = 5]) (by Kruskall-Wallis test, χ25
= 37.348; P |
| doi_str_mv | 10.1001/jama.287.13.1690 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_18465087</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><ama_id>194791</ama_id><sourcerecordid>113077022</sourcerecordid><originalsourceid>FETCH-LOGICAL-a468t-cf52a51bbfed1d41f2ee2666e9d475f5b727e172faaab1d374a0275f86f9941d3</originalsourceid><addsrcrecordid>eNpd0d1rFDEQAPAgij2r7_oioaBve2aS7CZ5PK8fFgotUhWfltndSbvHbvZMdpH-9wZ7UjAvCTO_GcIMY29BrEEI-LTDEdfSmjWoNVROPGMrKJUtVOnsc7YSwtnCaKuP2KuUdiIfUOYlOwJwsrJOrdj9JqWp7XHup8A_0_ybKPDtzxu5dfyCAs19y79j7DHMiWPo-Cbk0IR3y_C3pvhK-UEdv17mdhop8dMl9uGO_8Doc13gt_cUcf_wmr3wOCR6c7iP2bfzs9vtl-Lq-uJyu7kqUFd2LlpfSiyhaTx10GnwkkhWVUWu06b0ZWOkITDSI2IDnTIahcwJW3nndA4cs4-Pffdx-rVQmuuxTy0NAwaallSD1VUprMnw5D-4m5YY8t9qCaDyNEuV0fsDWpqRunof-xHjQ_1vgBl8OABMLQ4-Ymj79OTyJgwIl927R5c39pR12jhQfwD7RIg3</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>211369053</pqid></control><display><type>article</type><title>Association Between CYP2C9 Genetic Variants and Anticoagulation-Related Outcomes During Warfarin Therapy</title><source>MEDLINE</source><source>American Medical Association Journals</source><creator>Higashi, Mitchell K ; Veenstra, David L ; Kondo, L. Midori ; Wittkowsky, Ann K ; Srinouanprachanh, Sengkeo L ; Farin, Fred M ; Rettie, Allan E</creator><creatorcontrib>Higashi, Mitchell K ; Veenstra, David L ; Kondo, L. Midori ; Wittkowsky, Ann K ; Srinouanprachanh, Sengkeo L ; Farin, Fred M ; Rettie, Allan E</creatorcontrib><description>CONTEXT Warfarin is a commonly used anticoagulant that requires careful clinical
management to balance the risks of overanticoagulation and bleeding with those
of underanticoagulation and clotting. The principal enzyme involved in warfarin
metabolism is CYP2C9, and 2 relatively common variant forms with reduced activity
have been identified, CYP2C9*2 and CYP2C9*3. Patients with these genetic variants have been shown to require
lower maintenance doses of warfarin, but a direct association between CYP2C9
genotype and anticoagulation status or bleeding risk has not been established. OBJECTIVE To determine if CYP2C9*2 and CYP2C9*3 variants are associated with overanticoagulation and bleeding
events during warfarin therapy. DESIGN AND SETTING Retrospective cohort study conducted at 2 anticoagulation clinics based
in Seattle, Wash. PARTICIPANTS Two hundred patients receiving long-term warfarin therapy for various
indications during April 3, 1990, to May 31, 2001. Only patients with a complete
history of warfarin exposure were included. MAIN OUTCOME MEASURES Anticoagulation status, measured by time to therapeutic international
normalized ratio (INR), rate of above-range INRs, and time to stable warfarin
dosing; and time to serious or life-threatening bleeding events. RESULTS Among 185 patients with analyzable data, 58 (31.4%) had at least 1 variant
CYP2C9 allele and 127 (68.6%) had the wild-type (*1/*1)
genotype. Mean maintenance dose varied significantly among the 6 genotype
groups (*1/*1 [n = 127], *1/*2 [n = 28], *1/*3 [n = 18], *2/*2 [n = 4], *2/*3 [n = 3], *3/*3 [n = 5]) (by Kruskall-Wallis test, χ25
= 37.348; P<.001). Compared with patients with
the wild-type genotype, patients with at least 1 variant allele had an increased
risk of above-range INRs (hazard ratio [HR], 1.40; 95% confidence interval
[CI], 1.03-1.90). The variant group also required more time to achieve stable
dosing (HR, 0.65; 95% CI, 0.45-0.94), with a median difference of 95 days
(P = .004). In addition, although numbers were small
for some genotypes, representing potentially unstable estimates, patients
with a variant genotype had a significantly increased risk of a serious or
life-threatening bleeding event (HR, 2.39; 95% CI, 1.18-4.86). CONCLUSIONS The results of our study suggest that the CYP2C9*2 and CYP2C9*3 polymorphisms are associated
with an increased risk of overanticoagulation and of bleeding events among
patients in a warfarin anticoagulation clinic setting, although small numbers
in some cases would suggest the need for caution in interpretation. Screening
for CYP2C9 variants may allow clinicians to develop dosing protocols and surveillance
techniques to reduce the risk of adverse drug reactions in patients receiving
warfarin.</description><identifier>ISSN: 0098-7484</identifier><identifier>EISSN: 1538-3598</identifier><identifier>DOI: 10.1001/jama.287.13.1690</identifier><identifier>PMID: 11926893</identifier><identifier>CODEN: JAMAAP</identifier><language>eng</language><publisher>Chicago, IL: American Medical Association</publisher><subject>Aged ; Anticoagulants - administration & dosage ; Anticoagulants - adverse effects ; Anticoagulants - therapeutic use ; Aryl Hydrocarbon Hydroxylases ; Biological and medical sciences ; Blood Coagulation - genetics ; Blood. Blood coagulation. Reticuloendothelial system ; Cytochrome P-450 CYP2C9 ; Cytochrome P-450 Enzyme System - genetics ; Drug therapy ; Effectiveness ; Female ; Genetics ; Genotype ; Hemorrhage ; Humans ; International Normalized Ratio ; Male ; Medical sciences ; Middle Aged ; Pharmacology. Drug treatments ; Polymorphism, Genetic ; Proportional Hazards Models ; Retrospective Studies ; Risk ; Steroid 16-alpha-Hydroxylase ; Steroid Hydroxylases - genetics ; Warfarin - administration & dosage ; Warfarin - adverse effects ; Warfarin - therapeutic use</subject><ispartof>JAMA : the journal of the American Medical Association, 2002-04, Vol.287 (13), p.1690-1698</ispartof><rights>2002 INIST-CNRS</rights><rights>Copyright American Medical Association Apr 3, 2002</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a468t-cf52a51bbfed1d41f2ee2666e9d475f5b727e172faaab1d374a0275f86f9941d3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://jamanetwork.com/journals/jama/articlepdf/10.1001/jama.287.13.1690$$EPDF$$P50$$Gama$$H</linktopdf><linktohtml>$$Uhttps://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.287.13.1690$$EHTML$$P50$$Gama$$H</linktohtml><link.rule.ids>64,314,777,781,3327,27905,27906,76238,76241</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13597109$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11926893$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Higashi, Mitchell K</creatorcontrib><creatorcontrib>Veenstra, David L</creatorcontrib><creatorcontrib>Kondo, L. Midori</creatorcontrib><creatorcontrib>Wittkowsky, Ann K</creatorcontrib><creatorcontrib>Srinouanprachanh, Sengkeo L</creatorcontrib><creatorcontrib>Farin, Fred M</creatorcontrib><creatorcontrib>Rettie, Allan E</creatorcontrib><title>Association Between CYP2C9 Genetic Variants and Anticoagulation-Related Outcomes During Warfarin Therapy</title><title>JAMA : the journal of the American Medical Association</title><addtitle>JAMA</addtitle><description>CONTEXT Warfarin is a commonly used anticoagulant that requires careful clinical
management to balance the risks of overanticoagulation and bleeding with those
of underanticoagulation and clotting. The principal enzyme involved in warfarin
metabolism is CYP2C9, and 2 relatively common variant forms with reduced activity
have been identified, CYP2C9*2 and CYP2C9*3. Patients with these genetic variants have been shown to require
lower maintenance doses of warfarin, but a direct association between CYP2C9
genotype and anticoagulation status or bleeding risk has not been established. OBJECTIVE To determine if CYP2C9*2 and CYP2C9*3 variants are associated with overanticoagulation and bleeding
events during warfarin therapy. DESIGN AND SETTING Retrospective cohort study conducted at 2 anticoagulation clinics based
in Seattle, Wash. PARTICIPANTS Two hundred patients receiving long-term warfarin therapy for various
indications during April 3, 1990, to May 31, 2001. Only patients with a complete
history of warfarin exposure were included. MAIN OUTCOME MEASURES Anticoagulation status, measured by time to therapeutic international
normalized ratio (INR), rate of above-range INRs, and time to stable warfarin
dosing; and time to serious or life-threatening bleeding events. RESULTS Among 185 patients with analyzable data, 58 (31.4%) had at least 1 variant
CYP2C9 allele and 127 (68.6%) had the wild-type (*1/*1)
genotype. Mean maintenance dose varied significantly among the 6 genotype
groups (*1/*1 [n = 127], *1/*2 [n = 28], *1/*3 [n = 18], *2/*2 [n = 4], *2/*3 [n = 3], *3/*3 [n = 5]) (by Kruskall-Wallis test, χ25
= 37.348; P<.001). Compared with patients with
the wild-type genotype, patients with at least 1 variant allele had an increased
risk of above-range INRs (hazard ratio [HR], 1.40; 95% confidence interval
[CI], 1.03-1.90). The variant group also required more time to achieve stable
dosing (HR, 0.65; 95% CI, 0.45-0.94), with a median difference of 95 days
(P = .004). In addition, although numbers were small
for some genotypes, representing potentially unstable estimates, patients
with a variant genotype had a significantly increased risk of a serious or
life-threatening bleeding event (HR, 2.39; 95% CI, 1.18-4.86). CONCLUSIONS The results of our study suggest that the CYP2C9*2 and CYP2C9*3 polymorphisms are associated
with an increased risk of overanticoagulation and of bleeding events among
patients in a warfarin anticoagulation clinic setting, although small numbers
in some cases would suggest the need for caution in interpretation. Screening
for CYP2C9 variants may allow clinicians to develop dosing protocols and surveillance
techniques to reduce the risk of adverse drug reactions in patients receiving
warfarin.</description><subject>Aged</subject><subject>Anticoagulants - administration & dosage</subject><subject>Anticoagulants - adverse effects</subject><subject>Anticoagulants - therapeutic use</subject><subject>Aryl Hydrocarbon Hydroxylases</subject><subject>Biological and medical sciences</subject><subject>Blood Coagulation - genetics</subject><subject>Blood. Blood coagulation. Reticuloendothelial system</subject><subject>Cytochrome P-450 CYP2C9</subject><subject>Cytochrome P-450 Enzyme System - genetics</subject><subject>Drug therapy</subject><subject>Effectiveness</subject><subject>Female</subject><subject>Genetics</subject><subject>Genotype</subject><subject>Hemorrhage</subject><subject>Humans</subject><subject>International Normalized Ratio</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Pharmacology. Drug treatments</subject><subject>Polymorphism, Genetic</subject><subject>Proportional Hazards Models</subject><subject>Retrospective Studies</subject><subject>Risk</subject><subject>Steroid 16-alpha-Hydroxylase</subject><subject>Steroid Hydroxylases - genetics</subject><subject>Warfarin - administration & dosage</subject><subject>Warfarin - adverse effects</subject><subject>Warfarin - therapeutic use</subject><issn>0098-7484</issn><issn>1538-3598</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpd0d1rFDEQAPAgij2r7_oioaBve2aS7CZ5PK8fFgotUhWfltndSbvHbvZMdpH-9wZ7UjAvCTO_GcIMY29BrEEI-LTDEdfSmjWoNVROPGMrKJUtVOnsc7YSwtnCaKuP2KuUdiIfUOYlOwJwsrJOrdj9JqWp7XHup8A_0_ybKPDtzxu5dfyCAs19y79j7DHMiWPo-Cbk0IR3y_C3pvhK-UEdv17mdhop8dMl9uGO_8Doc13gt_cUcf_wmr3wOCR6c7iP2bfzs9vtl-Lq-uJyu7kqUFd2LlpfSiyhaTx10GnwkkhWVUWu06b0ZWOkITDSI2IDnTIahcwJW3nndA4cs4-Pffdx-rVQmuuxTy0NAwaallSD1VUprMnw5D-4m5YY8t9qCaDyNEuV0fsDWpqRunof-xHjQ_1vgBl8OABMLQ4-Ymj79OTyJgwIl927R5c39pR12jhQfwD7RIg3</recordid><startdate>20020403</startdate><enddate>20020403</enddate><creator>Higashi, Mitchell K</creator><creator>Veenstra, David L</creator><creator>Kondo, L. Midori</creator><creator>Wittkowsky, Ann K</creator><creator>Srinouanprachanh, Sengkeo L</creator><creator>Farin, Fred M</creator><creator>Rettie, Allan E</creator><general>American Medical Association</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7QL</scope><scope>7QP</scope><scope>7TK</scope><scope>7TS</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20020403</creationdate><title>Association Between CYP2C9 Genetic Variants and Anticoagulation-Related Outcomes During Warfarin Therapy</title><author>Higashi, Mitchell K ; Veenstra, David L ; Kondo, L. Midori ; Wittkowsky, Ann K ; Srinouanprachanh, Sengkeo L ; Farin, Fred M ; Rettie, Allan E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a468t-cf52a51bbfed1d41f2ee2666e9d475f5b727e172faaab1d374a0275f86f9941d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Aged</topic><topic>Anticoagulants - administration & dosage</topic><topic>Anticoagulants - adverse effects</topic><topic>Anticoagulants - therapeutic use</topic><topic>Aryl Hydrocarbon Hydroxylases</topic><topic>Biological and medical sciences</topic><topic>Blood Coagulation - genetics</topic><topic>Blood. Blood coagulation. Reticuloendothelial system</topic><topic>Cytochrome P-450 CYP2C9</topic><topic>Cytochrome P-450 Enzyme System - genetics</topic><topic>Drug therapy</topic><topic>Effectiveness</topic><topic>Female</topic><topic>Genetics</topic><topic>Genotype</topic><topic>Hemorrhage</topic><topic>Humans</topic><topic>International Normalized Ratio</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Pharmacology. Drug treatments</topic><topic>Polymorphism, Genetic</topic><topic>Proportional Hazards Models</topic><topic>Retrospective Studies</topic><topic>Risk</topic><topic>Steroid 16-alpha-Hydroxylase</topic><topic>Steroid Hydroxylases - genetics</topic><topic>Warfarin - administration & dosage</topic><topic>Warfarin - adverse effects</topic><topic>Warfarin - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Higashi, Mitchell K</creatorcontrib><creatorcontrib>Veenstra, David L</creatorcontrib><creatorcontrib>Kondo, L. Midori</creatorcontrib><creatorcontrib>Wittkowsky, Ann K</creatorcontrib><creatorcontrib>Srinouanprachanh, Sengkeo L</creatorcontrib><creatorcontrib>Farin, Fred M</creatorcontrib><creatorcontrib>Rettie, Allan E</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Physical Education Index</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>JAMA : the journal of the American Medical Association</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Higashi, Mitchell K</au><au>Veenstra, David L</au><au>Kondo, L. Midori</au><au>Wittkowsky, Ann K</au><au>Srinouanprachanh, Sengkeo L</au><au>Farin, Fred M</au><au>Rettie, Allan E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association Between CYP2C9 Genetic Variants and Anticoagulation-Related Outcomes During Warfarin Therapy</atitle><jtitle>JAMA : the journal of the American Medical Association</jtitle><addtitle>JAMA</addtitle><date>2002-04-03</date><risdate>2002</risdate><volume>287</volume><issue>13</issue><spage>1690</spage><epage>1698</epage><pages>1690-1698</pages><issn>0098-7484</issn><eissn>1538-3598</eissn><coden>JAMAAP</coden><abstract>CONTEXT Warfarin is a commonly used anticoagulant that requires careful clinical
management to balance the risks of overanticoagulation and bleeding with those
of underanticoagulation and clotting. The principal enzyme involved in warfarin
metabolism is CYP2C9, and 2 relatively common variant forms with reduced activity
have been identified, CYP2C9*2 and CYP2C9*3. Patients with these genetic variants have been shown to require
lower maintenance doses of warfarin, but a direct association between CYP2C9
genotype and anticoagulation status or bleeding risk has not been established. OBJECTIVE To determine if CYP2C9*2 and CYP2C9*3 variants are associated with overanticoagulation and bleeding
events during warfarin therapy. DESIGN AND SETTING Retrospective cohort study conducted at 2 anticoagulation clinics based
in Seattle, Wash. PARTICIPANTS Two hundred patients receiving long-term warfarin therapy for various
indications during April 3, 1990, to May 31, 2001. Only patients with a complete
history of warfarin exposure were included. MAIN OUTCOME MEASURES Anticoagulation status, measured by time to therapeutic international
normalized ratio (INR), rate of above-range INRs, and time to stable warfarin
dosing; and time to serious or life-threatening bleeding events. RESULTS Among 185 patients with analyzable data, 58 (31.4%) had at least 1 variant
CYP2C9 allele and 127 (68.6%) had the wild-type (*1/*1)
genotype. Mean maintenance dose varied significantly among the 6 genotype
groups (*1/*1 [n = 127], *1/*2 [n = 28], *1/*3 [n = 18], *2/*2 [n = 4], *2/*3 [n = 3], *3/*3 [n = 5]) (by Kruskall-Wallis test, χ25
= 37.348; P<.001). Compared with patients with
the wild-type genotype, patients with at least 1 variant allele had an increased
risk of above-range INRs (hazard ratio [HR], 1.40; 95% confidence interval
[CI], 1.03-1.90). The variant group also required more time to achieve stable
dosing (HR, 0.65; 95% CI, 0.45-0.94), with a median difference of 95 days
(P = .004). In addition, although numbers were small
for some genotypes, representing potentially unstable estimates, patients
with a variant genotype had a significantly increased risk of a serious or
life-threatening bleeding event (HR, 2.39; 95% CI, 1.18-4.86). CONCLUSIONS The results of our study suggest that the CYP2C9*2 and CYP2C9*3 polymorphisms are associated
with an increased risk of overanticoagulation and of bleeding events among
patients in a warfarin anticoagulation clinic setting, although small numbers
in some cases would suggest the need for caution in interpretation. Screening
for CYP2C9 variants may allow clinicians to develop dosing protocols and surveillance
techniques to reduce the risk of adverse drug reactions in patients receiving
warfarin.</abstract><cop>Chicago, IL</cop><pub>American Medical Association</pub><pmid>11926893</pmid><doi>10.1001/jama.287.13.1690</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0098-7484 |
| ispartof | JAMA : the journal of the American Medical Association, 2002-04, Vol.287 (13), p.1690-1698 |
| issn | 0098-7484 1538-3598 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_18465087 |
| source | MEDLINE; American Medical Association Journals |
| subjects | Aged Anticoagulants - administration & dosage Anticoagulants - adverse effects Anticoagulants - therapeutic use Aryl Hydrocarbon Hydroxylases Biological and medical sciences Blood Coagulation - genetics Blood. Blood coagulation. Reticuloendothelial system Cytochrome P-450 CYP2C9 Cytochrome P-450 Enzyme System - genetics Drug therapy Effectiveness Female Genetics Genotype Hemorrhage Humans International Normalized Ratio Male Medical sciences Middle Aged Pharmacology. Drug treatments Polymorphism, Genetic Proportional Hazards Models Retrospective Studies Risk Steroid 16-alpha-Hydroxylase Steroid Hydroxylases - genetics Warfarin - administration & dosage Warfarin - adverse effects Warfarin - therapeutic use |
| title | Association Between CYP2C9 Genetic Variants and Anticoagulation-Related Outcomes During Warfarin Therapy |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-19T01%3A31%3A13IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Association%20Between%20CYP2C9%20Genetic%20Variants%20and%20Anticoagulation-Related%20Outcomes%20During%20Warfarin%20Therapy&rft.jtitle=JAMA%20:%20the%20journal%20of%20the%20American%20Medical%20Association&rft.au=Higashi,%20Mitchell%20K&rft.date=2002-04-03&rft.volume=287&rft.issue=13&rft.spage=1690&rft.epage=1698&rft.pages=1690-1698&rft.issn=0098-7484&rft.eissn=1538-3598&rft.coden=JAMAAP&rft_id=info:doi/10.1001/jama.287.13.1690&rft_dat=%3Cproquest_pubme%3E113077022%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=211369053&rft_id=info:pmid/11926893&rft_ama_id=194791&rfr_iscdi=true |