Prothrombin G20210A Mutation Is Associated With Young-Onset Stroke: The Genetics of Early-Onset Stroke Study and Meta-Analysis
BACKGROUND AND PURPOSE—Although the prothrombin G20210A mutation has been implicated as a risk factor for venous thrombosis, its role in arterial ischemic stroke is unclear, particularly among young adults. To address this issue, we examined the association between prothrombin G20210A and ischemic s...
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| Veröffentlicht in: | Stroke (1970) 2014-04, Vol.45 (4), p.961-967 |
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| creator | Jiang, Baijia Ryan, Kathleen A Hamedani, Ali Cheng, Yuching Sparks, Mary J Koontz, Deborah Bean, Christopher J Gallagher, Margaret Hooper, W Craig McArdle, Patrick F O’Connell, Jeffrey R Stine, O Colin Wozniak, Marcella A Stern, Barney J Mitchell, Braxton D Kittner, Steven J Cole, John W |
| description | BACKGROUND AND PURPOSE—Although the prothrombin G20210A mutation has been implicated as a risk factor for venous thrombosis, its role in arterial ischemic stroke is unclear, particularly among young adults. To address this issue, we examined the association between prothrombin G20210A and ischemic stroke in a white case–control population and additionally performed a meta-analysis.
METHODS—From the population-based Genetics of Early Onset Stroke (GEOS) study, we identified 397 individuals of European ancestry aged 15 to 49 years with first-ever ischemic stroke and 426 matched controls. Logistic regression was used to calculate odds ratios (ORs) in the entire population and for subgroups stratified by sex, age, oral contraceptive use, migraine, and smoking status. A meta-analysis of 17 case–control studies (n=2305 cases |
| doi_str_mv | 10.1161/STROKEAHA.113.004063 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4049002</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1510401597</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3903-4733e5b47455bae8280ad94705c2b47fbaf588c8badd4a19dcfc9f5509fa19f63</originalsourceid><addsrcrecordid>eNp9kUFvFCEUx4nR2HX1GxjDxcTLVBhgFzyYTJp129hmjV1jPBGGgQ52FiowbfbSzy7Nrqu9eHr5w-89XvgB8BqjY4xn-P3l-uvq86I5bUokxwhRNCNPwASzmlZ0VvOnYIIQEVVNhTgCL1L6iRCqCWfPwVFNZ1gQwSfg_ksMuY9h0zoPlzWqMWrgxZhVdsHDswSblIJ2KpsOfne5hz_C6K-qlU8mw8scw7X5ANe9gUvjTXY6wWDhQsVh-4gpZey2UPkOXpisqsarYZtcegmeWTUk82pfp-Dbp8X65LQ6Xy3PTprzShOBSEXnhBjW0jllrFWG1xypTtA5Yroup7ZVlnGueau6jiosOm21sIwhYUuyMzIFH3dzb8Z2YzptfI5qkDfRbVTcyqCcfHzjXS-vwq2kiIqHb5uCd_sBMfwaTcpy45I2w6C8CWOSmOFiADMxLyjdoTqGlKKxh2cwkg_q5EFdiUTu1JW2N_-ueGj646oAb_eASloNNiqvXfrLcUoRR6JwfMfdhSGbmK6H8c5E2Rs15P7_O_wG4Ci1mA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1510401597</pqid></control><display><type>article</type><title>Prothrombin G20210A Mutation Is Associated With Young-Onset Stroke: The Genetics of Early-Onset Stroke Study and Meta-Analysis</title><source>MEDLINE</source><source>American Heart Association Journals</source><source>Journals@Ovid Complete</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Jiang, Baijia ; Ryan, Kathleen A ; Hamedani, Ali ; Cheng, Yuching ; Sparks, Mary J ; Koontz, Deborah ; Bean, Christopher J ; Gallagher, Margaret ; Hooper, W Craig ; McArdle, Patrick F ; O’Connell, Jeffrey R ; Stine, O Colin ; Wozniak, Marcella A ; Stern, Barney J ; Mitchell, Braxton D ; Kittner, Steven J ; Cole, John W</creator><creatorcontrib>Jiang, Baijia ; Ryan, Kathleen A ; Hamedani, Ali ; Cheng, Yuching ; Sparks, Mary J ; Koontz, Deborah ; Bean, Christopher J ; Gallagher, Margaret ; Hooper, W Craig ; McArdle, Patrick F ; O’Connell, Jeffrey R ; Stine, O Colin ; Wozniak, Marcella A ; Stern, Barney J ; Mitchell, Braxton D ; Kittner, Steven J ; Cole, John W</creatorcontrib><description>BACKGROUND AND PURPOSE—Although the prothrombin G20210A mutation has been implicated as a risk factor for venous thrombosis, its role in arterial ischemic stroke is unclear, particularly among young adults. To address this issue, we examined the association between prothrombin G20210A and ischemic stroke in a white case–control population and additionally performed a meta-analysis.
METHODS—From the population-based Genetics of Early Onset Stroke (GEOS) study, we identified 397 individuals of European ancestry aged 15 to 49 years with first-ever ischemic stroke and 426 matched controls. Logistic regression was used to calculate odds ratios (ORs) in the entire population and for subgroups stratified by sex, age, oral contraceptive use, migraine, and smoking status. A meta-analysis of 17 case–control studies (n=2305 cases <55 years) was also performed with and without GEOS data.
RESULTS—Within GEOS, the association of the prothrombin G20210A mutation with ischemic stroke did not achieve statistical significance (OR=2.5; 95% confidence interval [CI]=0.9–6.5; P=0.07). However, among adults aged 15 to 42 years (younger than median age), cases were significantly more likely than controls to have the mutation (OR=5.9; 95% CI=1.2–28.1; P=0.03), whereas adults aged 42 to 49 years were not (OR=1.4; 95% CI=0.4–5.1; P=0.94). In our meta-analysis, the mutation was associated with significantly increased stroke risk in adults ≤55 years (OR=1.4; 95% CI=1.1–1.9; P=0.02), with significance increasing with addition of the GEOS results (OR=1.5; 95% CI=1.1–2.0; P=0.005).
CONCLUSIONS—The prothrombin G20210A mutation is associated with ischemic stroke in young adults and may have an even stronger association among those with earlier onset strokes. Our finding of a stronger association in the younger young adult population requires replication.</description><identifier>ISSN: 0039-2499</identifier><identifier>EISSN: 1524-4628</identifier><identifier>DOI: 10.1161/STROKEAHA.113.004063</identifier><identifier>PMID: 24619398</identifier><identifier>CODEN: SJCCA7</identifier><language>eng</language><publisher>Hagerstown, MD: American Heart Association, Inc</publisher><subject>Adolescent ; Adult ; Age of Onset ; Biological and medical sciences ; Brain Ischemia - epidemiology ; Brain Ischemia - genetics ; Case-Control Studies ; European Continental Ancestry Group - statistics & numerical data ; Female ; Genetic Predisposition to Disease - epidemiology ; Genetic Predisposition to Disease - genetics ; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy ; Humans ; Logistic Models ; Male ; Medical sciences ; Middle Aged ; Nervous system (semeiology, syndromes) ; Neurology ; Point Mutation ; Prothrombin - genetics ; Risk Factors ; Stroke - epidemiology ; Stroke - genetics ; Vascular diseases and vascular malformations of the nervous system ; Young Adult</subject><ispartof>Stroke (1970), 2014-04, Vol.45 (4), p.961-967</ispartof><rights>2014 American Heart Association, Inc.</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3903-4733e5b47455bae8280ad94705c2b47fbaf588c8badd4a19dcfc9f5509fa19f63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,3687,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28440809$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24619398$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jiang, Baijia</creatorcontrib><creatorcontrib>Ryan, Kathleen A</creatorcontrib><creatorcontrib>Hamedani, Ali</creatorcontrib><creatorcontrib>Cheng, Yuching</creatorcontrib><creatorcontrib>Sparks, Mary J</creatorcontrib><creatorcontrib>Koontz, Deborah</creatorcontrib><creatorcontrib>Bean, Christopher J</creatorcontrib><creatorcontrib>Gallagher, Margaret</creatorcontrib><creatorcontrib>Hooper, W Craig</creatorcontrib><creatorcontrib>McArdle, Patrick F</creatorcontrib><creatorcontrib>O’Connell, Jeffrey R</creatorcontrib><creatorcontrib>Stine, O Colin</creatorcontrib><creatorcontrib>Wozniak, Marcella A</creatorcontrib><creatorcontrib>Stern, Barney J</creatorcontrib><creatorcontrib>Mitchell, Braxton D</creatorcontrib><creatorcontrib>Kittner, Steven J</creatorcontrib><creatorcontrib>Cole, John W</creatorcontrib><title>Prothrombin G20210A Mutation Is Associated With Young-Onset Stroke: The Genetics of Early-Onset Stroke Study and Meta-Analysis</title><title>Stroke (1970)</title><addtitle>Stroke</addtitle><description>BACKGROUND AND PURPOSE—Although the prothrombin G20210A mutation has been implicated as a risk factor for venous thrombosis, its role in arterial ischemic stroke is unclear, particularly among young adults. To address this issue, we examined the association between prothrombin G20210A and ischemic stroke in a white case–control population and additionally performed a meta-analysis.
METHODS—From the population-based Genetics of Early Onset Stroke (GEOS) study, we identified 397 individuals of European ancestry aged 15 to 49 years with first-ever ischemic stroke and 426 matched controls. Logistic regression was used to calculate odds ratios (ORs) in the entire population and for subgroups stratified by sex, age, oral contraceptive use, migraine, and smoking status. A meta-analysis of 17 case–control studies (n=2305 cases <55 years) was also performed with and without GEOS data.
RESULTS—Within GEOS, the association of the prothrombin G20210A mutation with ischemic stroke did not achieve statistical significance (OR=2.5; 95% confidence interval [CI]=0.9–6.5; P=0.07). However, among adults aged 15 to 42 years (younger than median age), cases were significantly more likely than controls to have the mutation (OR=5.9; 95% CI=1.2–28.1; P=0.03), whereas adults aged 42 to 49 years were not (OR=1.4; 95% CI=0.4–5.1; P=0.94). In our meta-analysis, the mutation was associated with significantly increased stroke risk in adults ≤55 years (OR=1.4; 95% CI=1.1–1.9; P=0.02), with significance increasing with addition of the GEOS results (OR=1.5; 95% CI=1.1–2.0; P=0.005).
CONCLUSIONS—The prothrombin G20210A mutation is associated with ischemic stroke in young adults and may have an even stronger association among those with earlier onset strokes. Our finding of a stronger association in the younger young adult population requires replication.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Age of Onset</subject><subject>Biological and medical sciences</subject><subject>Brain Ischemia - epidemiology</subject><subject>Brain Ischemia - genetics</subject><subject>Case-Control Studies</subject><subject>European Continental Ancestry Group - statistics & numerical data</subject><subject>Female</subject><subject>Genetic Predisposition to Disease - epidemiology</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy</subject><subject>Humans</subject><subject>Logistic Models</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Nervous system (semeiology, syndromes)</subject><subject>Neurology</subject><subject>Point Mutation</subject><subject>Prothrombin - genetics</subject><subject>Risk Factors</subject><subject>Stroke - epidemiology</subject><subject>Stroke - genetics</subject><subject>Vascular diseases and vascular malformations of the nervous system</subject><subject>Young Adult</subject><issn>0039-2499</issn><issn>1524-4628</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUFvFCEUx4nR2HX1GxjDxcTLVBhgFzyYTJp129hmjV1jPBGGgQ52FiowbfbSzy7Nrqu9eHr5w-89XvgB8BqjY4xn-P3l-uvq86I5bUokxwhRNCNPwASzmlZ0VvOnYIIQEVVNhTgCL1L6iRCqCWfPwVFNZ1gQwSfg_ksMuY9h0zoPlzWqMWrgxZhVdsHDswSblIJ2KpsOfne5hz_C6K-qlU8mw8scw7X5ANe9gUvjTXY6wWDhQsVh-4gpZey2UPkOXpisqsarYZtcegmeWTUk82pfp-Dbp8X65LQ6Xy3PTprzShOBSEXnhBjW0jllrFWG1xypTtA5Yroup7ZVlnGueau6jiosOm21sIwhYUuyMzIFH3dzb8Z2YzptfI5qkDfRbVTcyqCcfHzjXS-vwq2kiIqHb5uCd_sBMfwaTcpy45I2w6C8CWOSmOFiADMxLyjdoTqGlKKxh2cwkg_q5EFdiUTu1JW2N_-ueGj646oAb_eASloNNiqvXfrLcUoRR6JwfMfdhSGbmK6H8c5E2Rs15P7_O_wG4Ci1mA</recordid><startdate>201404</startdate><enddate>201404</enddate><creator>Jiang, Baijia</creator><creator>Ryan, Kathleen A</creator><creator>Hamedani, Ali</creator><creator>Cheng, Yuching</creator><creator>Sparks, Mary J</creator><creator>Koontz, Deborah</creator><creator>Bean, Christopher J</creator><creator>Gallagher, Margaret</creator><creator>Hooper, W Craig</creator><creator>McArdle, Patrick F</creator><creator>O’Connell, Jeffrey R</creator><creator>Stine, O Colin</creator><creator>Wozniak, Marcella A</creator><creator>Stern, Barney J</creator><creator>Mitchell, Braxton D</creator><creator>Kittner, Steven J</creator><creator>Cole, John W</creator><general>American Heart Association, Inc</general><general>Lippincott Williams & Wilkins</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201404</creationdate><title>Prothrombin G20210A Mutation Is Associated With Young-Onset Stroke: The Genetics of Early-Onset Stroke Study and Meta-Analysis</title><author>Jiang, Baijia ; Ryan, Kathleen A ; Hamedani, Ali ; Cheng, Yuching ; Sparks, Mary J ; Koontz, Deborah ; Bean, Christopher J ; Gallagher, Margaret ; Hooper, W Craig ; McArdle, Patrick F ; O’Connell, Jeffrey R ; Stine, O Colin ; Wozniak, Marcella A ; Stern, Barney J ; Mitchell, Braxton D ; Kittner, Steven J ; Cole, John W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3903-4733e5b47455bae8280ad94705c2b47fbaf588c8badd4a19dcfc9f5509fa19f63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Age of Onset</topic><topic>Biological and medical sciences</topic><topic>Brain Ischemia - epidemiology</topic><topic>Brain Ischemia - genetics</topic><topic>Case-Control Studies</topic><topic>European Continental Ancestry Group - statistics & numerical data</topic><topic>Female</topic><topic>Genetic Predisposition to Disease - epidemiology</topic><topic>Genetic Predisposition to Disease - genetics</topic><topic>Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy</topic><topic>Humans</topic><topic>Logistic Models</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Nervous system (semeiology, syndromes)</topic><topic>Neurology</topic><topic>Point Mutation</topic><topic>Prothrombin - genetics</topic><topic>Risk Factors</topic><topic>Stroke - epidemiology</topic><topic>Stroke - genetics</topic><topic>Vascular diseases and vascular malformations of the nervous system</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jiang, Baijia</creatorcontrib><creatorcontrib>Ryan, Kathleen A</creatorcontrib><creatorcontrib>Hamedani, Ali</creatorcontrib><creatorcontrib>Cheng, Yuching</creatorcontrib><creatorcontrib>Sparks, Mary J</creatorcontrib><creatorcontrib>Koontz, Deborah</creatorcontrib><creatorcontrib>Bean, Christopher J</creatorcontrib><creatorcontrib>Gallagher, Margaret</creatorcontrib><creatorcontrib>Hooper, W Craig</creatorcontrib><creatorcontrib>McArdle, Patrick F</creatorcontrib><creatorcontrib>O’Connell, Jeffrey R</creatorcontrib><creatorcontrib>Stine, O Colin</creatorcontrib><creatorcontrib>Wozniak, Marcella A</creatorcontrib><creatorcontrib>Stern, Barney J</creatorcontrib><creatorcontrib>Mitchell, Braxton D</creatorcontrib><creatorcontrib>Kittner, Steven J</creatorcontrib><creatorcontrib>Cole, John W</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>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Stroke (1970)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jiang, Baijia</au><au>Ryan, Kathleen A</au><au>Hamedani, Ali</au><au>Cheng, Yuching</au><au>Sparks, Mary J</au><au>Koontz, Deborah</au><au>Bean, Christopher J</au><au>Gallagher, Margaret</au><au>Hooper, W Craig</au><au>McArdle, Patrick F</au><au>O’Connell, Jeffrey R</au><au>Stine, O Colin</au><au>Wozniak, Marcella A</au><au>Stern, Barney J</au><au>Mitchell, Braxton D</au><au>Kittner, Steven J</au><au>Cole, John W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prothrombin G20210A Mutation Is Associated With Young-Onset Stroke: The Genetics of Early-Onset Stroke Study and Meta-Analysis</atitle><jtitle>Stroke (1970)</jtitle><addtitle>Stroke</addtitle><date>2014-04</date><risdate>2014</risdate><volume>45</volume><issue>4</issue><spage>961</spage><epage>967</epage><pages>961-967</pages><issn>0039-2499</issn><eissn>1524-4628</eissn><coden>SJCCA7</coden><abstract>BACKGROUND AND PURPOSE—Although the prothrombin G20210A mutation has been implicated as a risk factor for venous thrombosis, its role in arterial ischemic stroke is unclear, particularly among young adults. To address this issue, we examined the association between prothrombin G20210A and ischemic stroke in a white case–control population and additionally performed a meta-analysis.
METHODS—From the population-based Genetics of Early Onset Stroke (GEOS) study, we identified 397 individuals of European ancestry aged 15 to 49 years with first-ever ischemic stroke and 426 matched controls. Logistic regression was used to calculate odds ratios (ORs) in the entire population and for subgroups stratified by sex, age, oral contraceptive use, migraine, and smoking status. A meta-analysis of 17 case–control studies (n=2305 cases <55 years) was also performed with and without GEOS data.
RESULTS—Within GEOS, the association of the prothrombin G20210A mutation with ischemic stroke did not achieve statistical significance (OR=2.5; 95% confidence interval [CI]=0.9–6.5; P=0.07). However, among adults aged 15 to 42 years (younger than median age), cases were significantly more likely than controls to have the mutation (OR=5.9; 95% CI=1.2–28.1; P=0.03), whereas adults aged 42 to 49 years were not (OR=1.4; 95% CI=0.4–5.1; P=0.94). In our meta-analysis, the mutation was associated with significantly increased stroke risk in adults ≤55 years (OR=1.4; 95% CI=1.1–1.9; P=0.02), with significance increasing with addition of the GEOS results (OR=1.5; 95% CI=1.1–2.0; P=0.005).
CONCLUSIONS—The prothrombin G20210A mutation is associated with ischemic stroke in young adults and may have an even stronger association among those with earlier onset strokes. Our finding of a stronger association in the younger young adult population requires replication.</abstract><cop>Hagerstown, MD</cop><pub>American Heart Association, Inc</pub><pmid>24619398</pmid><doi>10.1161/STROKEAHA.113.004063</doi><tpages>7</tpages></addata></record> |
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| source | MEDLINE; American Heart Association Journals; Journals@Ovid Complete; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adolescent Adult Age of Onset Biological and medical sciences Brain Ischemia - epidemiology Brain Ischemia - genetics Case-Control Studies European Continental Ancestry Group - statistics & numerical data Female Genetic Predisposition to Disease - epidemiology Genetic Predisposition to Disease - genetics Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy Humans Logistic Models Male Medical sciences Middle Aged Nervous system (semeiology, syndromes) Neurology Point Mutation Prothrombin - genetics Risk Factors Stroke - epidemiology Stroke - genetics Vascular diseases and vascular malformations of the nervous system Young Adult |
| title | Prothrombin G20210A Mutation Is Associated With Young-Onset Stroke: The Genetics of Early-Onset Stroke Study and Meta-Analysis |
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