{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T10:10:11Z","timestamp":1760955011931,"version":"3.40.4"},"reference-count":25,"publisher":"S. Karger AG","issue":"6","license":[{"start":{"date-parts":[[2007,1,1]],"date-time":"2007-01-01T00:00:00Z","timestamp":1167609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2007,1,1]],"date-time":"2007-01-01T00:00:00Z","timestamp":1167609600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cerebrovasc Dis"],"published-print":{"date-parts":[[2007]]},"abstract":"<i>Background:<\/i> Signaling through estrogen receptor alpha (ER\u03b1) regulates vasodilatation and atherogenesis. Since hypertension and atherosclerosis are major mechanisms in stroke development, we hypothesized that genetic variants of the ER\u03b1 gene <i>(ESR1)<\/i> are determinants of future ischemic stroke or intracerebral hemorrhage (ICH). <i>Methods:<\/i> In a population-based prospective nested case-control study, the relationships between <i>ESR1<\/i> polymorphisms (<i>c.454\u2013397T<\/i>><i>C<\/i> and <i>c.454\u2013351A<\/i>><i>G<\/i>) and ischemic stroke and ICH were examined in univariate and multivariate models using conditional logistic regression, which included established risk factors.Definitive first-ever stroke events (n = 388), including ischemic stroke (n = 320), ICH (n = 61), and unspecified stroke (n = 7) cases, and controls without cardiovascular disease (n = 773), matched for age, sex, and geographical region were included. <i>Results:<\/i> Carriers of the <i>c.454\u2013397T\/T<\/i> genotype had a significantly (p = 0.017) increased risk of ICH (OR 2.31, 95% CI 1.16\u20134.60) in a univariate analysis. This association persisted (OR 3.94, 95% CI 1.54\u201310.03), after adjustment for stroke risk determinants. Carriers of <i>c.454\u2013397T\/T <\/i>or<i> c.454\u2013397T\/C <\/i>genotypeshad significantly (p = 0.002 and p = 0.004, respectively) higher mean systolic blood pressure (SBP), than carriers of <i>c.454\u2013397C\/C<\/i>, and a similar relationship was observed for diastolic blood pressure (DBP). The combinations of <i>c.454\u2013397T\/T<\/i> genotype and hypertension (OR 21.46, 95% CI 5.20\u201388.51), or high SBP (OR 18.17, 95% CI 4.91\u201367.31) or DBP (OR 11.94, 95% CI 3.75\u201338.03), were strongly associated with increased risk of ICH. <i>Conclusions:<\/i> In this population,the <i>c.454\u2013397T\/T<\/i> genotype associates with first-ever ICH, particularly in combination with hypertension. This implies that alterations in ER\u03b1-mediated signaling may be involved in the pathophysiology of this disease, with a putative impact on primary prevention.<\/jats:p>","DOI":"10.1159\/000110419","type":"journal-article","created":{"date-parts":[[2007,10,31]],"date-time":"2007-10-31T14:57:57Z","timestamp":1193842677000},"page":"500-508","source":"Crossref","is-referenced-by-count":10,"title":["Estrogen Receptor Alpha Gene Polymorphisms and First-Ever Intracerebral Hemorrhage"],"prefix":"10.1159","volume":"24","author":[{"given":"Magnus","family":"Strand","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingegerd","family":"S\u00f6derstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Per-Gunnar","family":"Wiklund","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00f6ran","family":"Hallmans","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"Weinehall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"S\u00f6derberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tommy","family":"Olsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2007,10,29]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016%2FS0002-9149%2802%2902405-0"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1016%2FS0002-9149%2802%2902418-9"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1161%2Fhh0402.105096"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1161%2F01.CIR.0000016173.98826.88"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1001%2Fjama.291.24.2969"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1097%2F00004872-200406000-00013"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1210%2Fjc.2005-0670"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1046%2Fj.1365-2796.2003.01179.x"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1530%2Feje.1.01973"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1080%2F14034950310001441"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1080%2F028134398750003133"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1046%2Fj.1365-2796.1996.431782000.x"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1056%2FNEJM199906103402306"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1056%2FNEJMoa012952"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1517%2Fphgs.4.3.269.22686"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1007%2Fs00109-001-0311-5"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1001%2Fjama.290.17.2263"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1001%2Fjama.290.17.2317"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1161%2F01.STR.0000181088.76518.ec"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1056%2FNEJM199410203311604"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1001%2Farchinte.153.10.1201"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1001%2Farchinte.153.1.73"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1001%2Fjama.288.3.321"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1056%2FNEJMoa010534"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1001%2Fjama.289.20.2673"}],"container-title":["Cerebrovascular Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/110419","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/110419","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T02:05:18Z","timestamp":1745460318000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000110419"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007]]},"references-count":25,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2007,12,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000110419","archive":["Portico"],"relation":{},"ISSN":["1015-9770","1421-9786"],"issn-type":[{"type":"print","value":"1015-9770"},{"type":"electronic","value":"1421-9786"}],"subject":[],"published":{"date-parts":[[2007]]}}}