{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T13:09:28Z","timestamp":1785330568681,"version":"3.55.0"},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,5,10]],"date-time":"2019-05-10T00:00:00Z","timestamp":1557446400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The potential effect of matrix metalloproteinase\u20109 (<jats:italic>MMP\u20109<\/jats:italic>) variants and these variants interactions on hemorrhagic transformation (HT) risk after ischemic stroke (IS) remain unclear. The aims of present study were to investigate the associations of six variants in <jats:italic>MMP\u20109<\/jats:italic> with HT, and these variants interactions whether related to increased HT risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>A total of 705 patients with IS who were admitted to the participating hospitals within 48\u00a0hr of symptom onset were consecutively enrolled between March 2014 and December 2016. HT was confirmed by brain computed tomography (CT) scan during 14\u00a0days from stroke onset. Six variants of <jats:italic>MMP\u20109<\/jats:italic> gene were measured by mass spectrometry. Interactions of gene variant\u2013gene variant were assessed through generalized multifactor dimensionality reduction method (GMDR).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>HT occurred in 104 (14.8%) patients. There were no differences in genotypes for the six variants between patients with and without HT using univariate analysis (all <jats:italic>p<\/jats:italic>\u00a0&gt;\u00a00.05). GMDR analysis revealed that there was a synergistic effect of gene variant\u2013gene variant interactions between rs3918242 and rs3787268 in <jats:italic>MMP\u20109<\/jats:italic> gene. Cox regression analysis showed that high\u2010risk interactions of rs3918242 and rs3787268 were associated with increased risk of HT after adjusting for covariates (hazard ratio: 2.08; 95% confidence interval: 1.34\u20137.85; <jats:italic>p\u00a0=\u00a0<\/jats:italic>0.016).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Incidence of HT is common in acute IS in Chinese population. The mechanisms leading to HT are most likely multifactorial. Two\u2010loci interactions of rs3918242 and rs3787268 in <jats:italic>MMP\u20109<\/jats:italic> gene may confer a higher risk for HT.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.1294","type":"journal-article","created":{"date-parts":[[2019,5,10]],"date-time":"2019-05-10T11:37:41Z","timestamp":1557488261000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Variants in matrix metalloproteinase\u20109 gene are associated with hemorrhagic transformation in acute ischemic stroke patients with atherothrombosis, small artery disease, and cardioembolic stroke"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1901-5486","authenticated-orcid":false,"given":"Xingyang","family":"Yi","sequence":"first","affiliation":[{"name":"Department of Neurology People\u2019s Hospital of Deyang City Deyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo","family":"Sui","sequence":"additional","affiliation":[{"name":"Nursing Department People\u2019s Hospital of Deyang City Deyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Neurology The Third Affiliated Hospital of Wenzhou Medical University Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology People\u2019s Hospital of Deyang City Deyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neurology The Third Affiliated Hospital of Wenzhou Medical University Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenxiao","family":"Chai","sequence":"additional","affiliation":[{"name":"Department of Neurology The Third Affiliated Hospital of Wenzhou Medical University Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Neurology People\u2019s Hospital of Deyang City Deyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,5,10]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09298"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21174"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.109.570515"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.110.604199"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.112.665760"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000058700.41738.12"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.106.481556"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1086\/338759"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2012.11"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/01616412.1999.11740948"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000098059"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000061888.71524.DF"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0125397"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.135318"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.113.004627"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2013.203"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.107.488189"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1161\/STR.0000000000000024"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000254524.23708.c9"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.28.5.957"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A0539"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2012.05.031"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1086\/518312"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2008.12.020"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2007.12.003"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000098648.54429.1C"},{"key":"e_1_2_9_28_1","first-page":"400","article-title":"Correlations between MMP\u20102\/MMP\u20109 promoter polymorphisms and ischemic stroke","volume":"7","author":"Nie S. 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