Interleukin-6 Gene -174 G/C Promoter Polymorphism Predicts Severity and Outcome in Acute Ischemic Stroke Patients from North India
Background A guanine/cytosine (G/C) substitution occurring in position -174 of the interleukin-6 (IL-6) gene promoter changes the expression of IL-6 circulating proteins. We evaluated the occurrence of IL-6 -174 G/C polymorphism in patients with acute ischemic stroke and studied its association with...
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| Veröffentlicht in: | Journal of stroke and cerebrovascular diseases 2013-07, Vol.22 (5), p.683-689 |
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| creator | Chakraborty, Baidarbhi, MD Chowdhury, Debashish, MD, DM Vishnoi, Gaurav, MD Goswami, Binita, MD Kishore, Jugal, MD Agarwal, Sarita, MD |
| description | Background A guanine/cytosine (G/C) substitution occurring in position -174 of the interleukin-6 (IL-6) gene promoter changes the expression of IL-6 circulating proteins. We evaluated the occurrence of IL-6 -174 G/C polymorphism in patients with acute ischemic stroke and studied its association with stroke severity, outcome, and mortality. Methods One hundred patients with acute ischemic stroke and 120 age and sex-matched healthy controls were studied. Genotyping was performed using polymerase chain reaction and restriction enzyme analysis. Serum levels of IL-6 were measured using enzyme-linked immunosorbent assay. Stroke was classified using Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Severity was assessed by the National Institutes of Health Stroke Scale. Outcome measures included modified Rankin Scale (mRS) and Barthel Index (BI) scores at 7 days and 3 and 6 months. Mortality/survival was assessed using the Kaplan–Meier analysis. Results The frequency of GG, GC, and CC genotypes did not differ significantly between cases and controls. No association was seen between TOAST subtype and genotype. At the time of admission, stroke was more severe in patients with the GC genotype ( P = .03) and less severe in the GG genotype ( P = .04). The GC genotype was also associated with higher serum IL-6 levels and poor short-term (BI P = .001; mRS P = .003) and long-term outcomes (BI P = 9 × 10−5 ; mRS P = 9 × 10−5 ), while the GG genotype had significantly lower serum IL-6 levels and better short and long-term outcomes (BI P = 3 × 10−5 ; mRS P = 2 × 10−4 ). There was significantly lesser mortality in the GG genotype and more in the GC genotype based on the Kaplan–Meier analysis. Conclusions Patients with the GC genotype had more severe strokes with poorer short and long-term outcomes and increased mortality. The GG genotype was associated with less severe strokes, better short and long-term prognosis, and survival. The GG genotype appears to be protective against stroke severity, outcome, and mortality. |
| doi_str_mv | 10.1016/j.jstrokecerebrovasdis.2012.02.007 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1381102328</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1052305712000444</els_id><sourcerecordid>1381102328</sourcerecordid><originalsourceid>FETCH-LOGICAL-c459t-cccc903f2bd7f135d049fc8cfd067503503361f00dee429e03b41164c31ed4253</originalsourceid><addsrcrecordid>eNqVUt-LEzEQXkTxztN_QfIowvZm8mO3fRHOctZC8QrV57BNZmna3c2ZZAt99S83tacP4ovhgwzJN98k30xRvEeYIGB1u5_sYwr-QIYCbYM_NtG6OOGAfAIZUD8rrlEJXk4V4vMcg-KlAFVfFa9i3AMgqql6WVxxLhEqpa6LH8shUehoPLihrNiCBmIl1pItbudsHXzv8zVb--7U-_C4c7HPp2SdSZFt6EjBpRNrBssexmR8T8wN7M6Midgymh31zrDNrzezdZMcDTmtzarsiw9px5aDdc3r4kXbdJHePO03xbdP91_nn8vVw2I5v1uVRqpZKk1eMxAt39q6RaEsyFlrpqa1UNUKRIaosAWwRJLPCMRWIlbSCCQruRI3xbuL7mPw30eKSfcuGuq6ZiA_Ro1iighc8GmmfrxQTfAxBmr1Y3B9E04aQZ97off6X73Q515oyIA6i7x9qjdue7J_JH6bnwmrC4Hyr4-Ogo4mW2SyvYFM0ta7_6v34S8507nBmaY70Ini3o9hyP5q1DEn6M15Os7DgRwApJTiJwuwve0</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1381102328</pqid></control><display><type>article</type><title>Interleukin-6 Gene -174 G/C Promoter Polymorphism Predicts Severity and Outcome in Acute Ischemic Stroke Patients from North India</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Chakraborty, Baidarbhi, MD ; Chowdhury, Debashish, MD, DM ; Vishnoi, Gaurav, MD ; Goswami, Binita, MD ; Kishore, Jugal, MD ; Agarwal, Sarita, MD</creator><creatorcontrib>Chakraborty, Baidarbhi, MD ; Chowdhury, Debashish, MD, DM ; Vishnoi, Gaurav, MD ; Goswami, Binita, MD ; Kishore, Jugal, MD ; Agarwal, Sarita, MD</creatorcontrib><description>Background A guanine/cytosine (G/C) substitution occurring in position -174 of the interleukin-6 (IL-6) gene promoter changes the expression of IL-6 circulating proteins. We evaluated the occurrence of IL-6 -174 G/C polymorphism in patients with acute ischemic stroke and studied its association with stroke severity, outcome, and mortality. Methods One hundred patients with acute ischemic stroke and 120 age and sex-matched healthy controls were studied. Genotyping was performed using polymerase chain reaction and restriction enzyme analysis. Serum levels of IL-6 were measured using enzyme-linked immunosorbent assay. Stroke was classified using Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Severity was assessed by the National Institutes of Health Stroke Scale. Outcome measures included modified Rankin Scale (mRS) and Barthel Index (BI) scores at 7 days and 3 and 6 months. Mortality/survival was assessed using the Kaplan–Meier analysis. Results The frequency of GG, GC, and CC genotypes did not differ significantly between cases and controls. No association was seen between TOAST subtype and genotype. At the time of admission, stroke was more severe in patients with the GC genotype ( P = .03) and less severe in the GG genotype ( P = .04). The GC genotype was also associated with higher serum IL-6 levels and poor short-term (BI P = .001; mRS P = .003) and long-term outcomes (BI P = 9 × 10−5 ; mRS P = 9 × 10−5 ), while the GG genotype had significantly lower serum IL-6 levels and better short and long-term outcomes (BI P = 3 × 10−5 ; mRS P = 2 × 10−4 ). There was significantly lesser mortality in the GG genotype and more in the GC genotype based on the Kaplan–Meier analysis. Conclusions Patients with the GC genotype had more severe strokes with poorer short and long-term outcomes and increased mortality. The GG genotype was associated with less severe strokes, better short and long-term prognosis, and survival. The GG genotype appears to be protective against stroke severity, outcome, and mortality.</description><identifier>ISSN: 1052-3057</identifier><identifier>EISSN: 1532-8511</identifier><identifier>DOI: 10.1016/j.jstrokecerebrovasdis.2012.02.007</identifier><identifier>PMID: 22410655</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Brain Ischemia - diagnosis ; Brain Ischemia - ethnology ; Brain Ischemia - genetics ; Brain Ischemia - immunology ; Brain Ischemia - mortality ; Cardiovascular ; Case-Control Studies ; Chi-Square Distribution ; Disability Evaluation ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genetics ; Humans ; India - epidemiology ; interleukin-6 ; Interleukin-6 - blood ; Interleukin-6 - genetics ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neurology ; Odds Ratio ; outcome ; Phenotype ; polymorphism ; Polymorphism, Genetic ; Predictive Value of Tests ; Prognosis ; Promoter Regions, Genetic ; Risk Assessment ; Risk Factors ; Severity of Illness Index ; stroke ; Stroke - diagnosis ; Stroke - ethnology ; Stroke - genetics ; Stroke - immunology ; Stroke - mortality ; Young Adult</subject><ispartof>Journal of stroke and cerebrovascular diseases, 2013-07, Vol.22 (5), p.683-689</ispartof><rights>National Stroke Association</rights><rights>2013 National Stroke Association</rights><rights>Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c459t-cccc903f2bd7f135d049fc8cfd067503503361f00dee429e03b41164c31ed4253</citedby><cites>FETCH-LOGICAL-c459t-cccc903f2bd7f135d049fc8cfd067503503361f00dee429e03b41164c31ed4253</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1052305712000444$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22410655$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chakraborty, Baidarbhi, MD</creatorcontrib><creatorcontrib>Chowdhury, Debashish, MD, DM</creatorcontrib><creatorcontrib>Vishnoi, Gaurav, MD</creatorcontrib><creatorcontrib>Goswami, Binita, MD</creatorcontrib><creatorcontrib>Kishore, Jugal, MD</creatorcontrib><creatorcontrib>Agarwal, Sarita, MD</creatorcontrib><title>Interleukin-6 Gene -174 G/C Promoter Polymorphism Predicts Severity and Outcome in Acute Ischemic Stroke Patients from North India</title><title>Journal of stroke and cerebrovascular diseases</title><addtitle>J Stroke Cerebrovasc Dis</addtitle><description>Background A guanine/cytosine (G/C) substitution occurring in position -174 of the interleukin-6 (IL-6) gene promoter changes the expression of IL-6 circulating proteins. We evaluated the occurrence of IL-6 -174 G/C polymorphism in patients with acute ischemic stroke and studied its association with stroke severity, outcome, and mortality. Methods One hundred patients with acute ischemic stroke and 120 age and sex-matched healthy controls were studied. Genotyping was performed using polymerase chain reaction and restriction enzyme analysis. Serum levels of IL-6 were measured using enzyme-linked immunosorbent assay. Stroke was classified using Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Severity was assessed by the National Institutes of Health Stroke Scale. Outcome measures included modified Rankin Scale (mRS) and Barthel Index (BI) scores at 7 days and 3 and 6 months. Mortality/survival was assessed using the Kaplan–Meier analysis. Results The frequency of GG, GC, and CC genotypes did not differ significantly between cases and controls. No association was seen between TOAST subtype and genotype. At the time of admission, stroke was more severe in patients with the GC genotype ( P = .03) and less severe in the GG genotype ( P = .04). The GC genotype was also associated with higher serum IL-6 levels and poor short-term (BI P = .001; mRS P = .003) and long-term outcomes (BI P = 9 × 10−5 ; mRS P = 9 × 10−5 ), while the GG genotype had significantly lower serum IL-6 levels and better short and long-term outcomes (BI P = 3 × 10−5 ; mRS P = 2 × 10−4 ). There was significantly lesser mortality in the GG genotype and more in the GC genotype based on the Kaplan–Meier analysis. Conclusions Patients with the GC genotype had more severe strokes with poorer short and long-term outcomes and increased mortality. The GG genotype was associated with less severe strokes, better short and long-term prognosis, and survival. The GG genotype appears to be protective against stroke severity, outcome, and mortality.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Brain Ischemia - diagnosis</subject><subject>Brain Ischemia - ethnology</subject><subject>Brain Ischemia - genetics</subject><subject>Brain Ischemia - immunology</subject><subject>Brain Ischemia - mortality</subject><subject>Cardiovascular</subject><subject>Case-Control Studies</subject><subject>Chi-Square Distribution</subject><subject>Disability Evaluation</subject><subject>Female</subject><subject>Gene Frequency</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetics</subject><subject>Humans</subject><subject>India - epidemiology</subject><subject>interleukin-6</subject><subject>Interleukin-6 - blood</subject><subject>Interleukin-6 - genetics</subject><subject>Kaplan-Meier Estimate</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neurology</subject><subject>Odds Ratio</subject><subject>outcome</subject><subject>Phenotype</subject><subject>polymorphism</subject><subject>Polymorphism, Genetic</subject><subject>Predictive Value of Tests</subject><subject>Prognosis</subject><subject>Promoter Regions, Genetic</subject><subject>Risk Assessment</subject><subject>Risk Factors</subject><subject>Severity of Illness Index</subject><subject>stroke</subject><subject>Stroke - diagnosis</subject><subject>Stroke - ethnology</subject><subject>Stroke - genetics</subject><subject>Stroke - immunology</subject><subject>Stroke - mortality</subject><subject>Young Adult</subject><issn>1052-3057</issn><issn>1532-8511</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVUt-LEzEQXkTxztN_QfIowvZm8mO3fRHOctZC8QrV57BNZmna3c2ZZAt99S83tacP4ovhgwzJN98k30xRvEeYIGB1u5_sYwr-QIYCbYM_NtG6OOGAfAIZUD8rrlEJXk4V4vMcg-KlAFVfFa9i3AMgqql6WVxxLhEqpa6LH8shUehoPLihrNiCBmIl1pItbudsHXzv8zVb--7U-_C4c7HPp2SdSZFt6EjBpRNrBssexmR8T8wN7M6Midgymh31zrDNrzezdZMcDTmtzarsiw9px5aDdc3r4kXbdJHePO03xbdP91_nn8vVw2I5v1uVRqpZKk1eMxAt39q6RaEsyFlrpqa1UNUKRIaosAWwRJLPCMRWIlbSCCQruRI3xbuL7mPw30eKSfcuGuq6ZiA_Ro1iighc8GmmfrxQTfAxBmr1Y3B9E04aQZ97off6X73Q515oyIA6i7x9qjdue7J_JH6bnwmrC4Hyr4-Ogo4mW2SyvYFM0ta7_6v34S8507nBmaY70Ini3o9hyP5q1DEn6M15Os7DgRwApJTiJwuwve0</recordid><startdate>20130701</startdate><enddate>20130701</enddate><creator>Chakraborty, Baidarbhi, MD</creator><creator>Chowdhury, Debashish, MD, DM</creator><creator>Vishnoi, Gaurav, MD</creator><creator>Goswami, Binita, MD</creator><creator>Kishore, Jugal, MD</creator><creator>Agarwal, Sarita, MD</creator><general>Elsevier Inc</general><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></search><sort><creationdate>20130701</creationdate><title>Interleukin-6 Gene -174 G/C Promoter Polymorphism Predicts Severity and Outcome in Acute Ischemic Stroke Patients from North India</title><author>Chakraborty, Baidarbhi, MD ; Chowdhury, Debashish, MD, DM ; Vishnoi, Gaurav, MD ; Goswami, Binita, MD ; Kishore, Jugal, MD ; Agarwal, Sarita, MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c459t-cccc903f2bd7f135d049fc8cfd067503503361f00dee429e03b41164c31ed4253</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Brain Ischemia - diagnosis</topic><topic>Brain Ischemia - ethnology</topic><topic>Brain Ischemia - genetics</topic><topic>Brain Ischemia - immunology</topic><topic>Brain Ischemia - mortality</topic><topic>Cardiovascular</topic><topic>Case-Control Studies</topic><topic>Chi-Square Distribution</topic><topic>Disability Evaluation</topic><topic>Female</topic><topic>Gene Frequency</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetics</topic><topic>Humans</topic><topic>India - epidemiology</topic><topic>interleukin-6</topic><topic>Interleukin-6 - blood</topic><topic>Interleukin-6 - genetics</topic><topic>Kaplan-Meier Estimate</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neurology</topic><topic>Odds Ratio</topic><topic>outcome</topic><topic>Phenotype</topic><topic>polymorphism</topic><topic>Polymorphism, Genetic</topic><topic>Predictive Value of Tests</topic><topic>Prognosis</topic><topic>Promoter Regions, Genetic</topic><topic>Risk Assessment</topic><topic>Risk Factors</topic><topic>Severity of Illness Index</topic><topic>stroke</topic><topic>Stroke - diagnosis</topic><topic>Stroke - ethnology</topic><topic>Stroke - genetics</topic><topic>Stroke - immunology</topic><topic>Stroke - mortality</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chakraborty, Baidarbhi, MD</creatorcontrib><creatorcontrib>Chowdhury, Debashish, MD, DM</creatorcontrib><creatorcontrib>Vishnoi, Gaurav, MD</creatorcontrib><creatorcontrib>Goswami, Binita, MD</creatorcontrib><creatorcontrib>Kishore, Jugal, MD</creatorcontrib><creatorcontrib>Agarwal, Sarita, MD</creatorcontrib><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><jtitle>Journal of stroke and cerebrovascular diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chakraborty, Baidarbhi, MD</au><au>Chowdhury, Debashish, MD, DM</au><au>Vishnoi, Gaurav, MD</au><au>Goswami, Binita, MD</au><au>Kishore, Jugal, MD</au><au>Agarwal, Sarita, MD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interleukin-6 Gene -174 G/C Promoter Polymorphism Predicts Severity and Outcome in Acute Ischemic Stroke Patients from North India</atitle><jtitle>Journal of stroke and cerebrovascular diseases</jtitle><addtitle>J Stroke Cerebrovasc Dis</addtitle><date>2013-07-01</date><risdate>2013</risdate><volume>22</volume><issue>5</issue><spage>683</spage><epage>689</epage><pages>683-689</pages><issn>1052-3057</issn><eissn>1532-8511</eissn><abstract>Background A guanine/cytosine (G/C) substitution occurring in position -174 of the interleukin-6 (IL-6) gene promoter changes the expression of IL-6 circulating proteins. We evaluated the occurrence of IL-6 -174 G/C polymorphism in patients with acute ischemic stroke and studied its association with stroke severity, outcome, and mortality. Methods One hundred patients with acute ischemic stroke and 120 age and sex-matched healthy controls were studied. Genotyping was performed using polymerase chain reaction and restriction enzyme analysis. Serum levels of IL-6 were measured using enzyme-linked immunosorbent assay. Stroke was classified using Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Severity was assessed by the National Institutes of Health Stroke Scale. Outcome measures included modified Rankin Scale (mRS) and Barthel Index (BI) scores at 7 days and 3 and 6 months. Mortality/survival was assessed using the Kaplan–Meier analysis. Results The frequency of GG, GC, and CC genotypes did not differ significantly between cases and controls. No association was seen between TOAST subtype and genotype. At the time of admission, stroke was more severe in patients with the GC genotype ( P = .03) and less severe in the GG genotype ( P = .04). The GC genotype was also associated with higher serum IL-6 levels and poor short-term (BI P = .001; mRS P = .003) and long-term outcomes (BI P = 9 × 10−5 ; mRS P = 9 × 10−5 ), while the GG genotype had significantly lower serum IL-6 levels and better short and long-term outcomes (BI P = 3 × 10−5 ; mRS P = 2 × 10−4 ). There was significantly lesser mortality in the GG genotype and more in the GC genotype based on the Kaplan–Meier analysis. Conclusions Patients with the GC genotype had more severe strokes with poorer short and long-term outcomes and increased mortality. The GG genotype was associated with less severe strokes, better short and long-term prognosis, and survival. The GG genotype appears to be protective against stroke severity, outcome, and mortality.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>22410655</pmid><doi>10.1016/j.jstrokecerebrovasdis.2012.02.007</doi><tpages>7</tpages></addata></record> |
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| subjects | Adult Aged Aged, 80 and over Brain Ischemia - diagnosis Brain Ischemia - ethnology Brain Ischemia - genetics Brain Ischemia - immunology Brain Ischemia - mortality Cardiovascular Case-Control Studies Chi-Square Distribution Disability Evaluation Female Gene Frequency Genetic Predisposition to Disease Genetics Humans India - epidemiology interleukin-6 Interleukin-6 - blood Interleukin-6 - genetics Kaplan-Meier Estimate Male Middle Aged Neurology Odds Ratio outcome Phenotype polymorphism Polymorphism, Genetic Predictive Value of Tests Prognosis Promoter Regions, Genetic Risk Assessment Risk Factors Severity of Illness Index stroke Stroke - diagnosis Stroke - ethnology Stroke - genetics Stroke - immunology Stroke - mortality Young Adult |
| title | Interleukin-6 Gene -174 G/C Promoter Polymorphism Predicts Severity and Outcome in Acute Ischemic Stroke Patients from North India |
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