{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:08:06Z","timestamp":1753891686905,"version":"3.41.2"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T00:00:00Z","timestamp":1622160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Platelet endothelial aggregation receptor-1 (PEAR1) rs12041331 has been reported to affect agonist-stimulated platelet aggregation, but it remains unclear whether this variant plays a role in recurrent stroke. Here we assess the clinical relevance of PEAR1 rs12041331 in acute minor ischemic stroke (AMIS) and transient ischemic attack (TIA) Chinese patients treated with dual antiplatelet therapy (DAPT).<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> We recruited 273 consecutive minor stroke and TIA patients, and Cox proportional hazard regression was used to model the relationship between PEAR1 rs12041331 and thrombotic and bleeding events.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Genotyping for PEAR1 rs12041331 showed 49 (18.0%) AA homozygotes, 129 (47.3%) GA heterozygotes, and 95 (34.7%) GG homozygotes. No association was observed between PEAR1 rs12041331 genotype and stroke or composite clinical vascular event rates (ischemic stroke, hemorrhagic stroke, TIA, myocardial infarction, or vascular death) or bleeding events regardless if individuals carried one or two copies of the A allele. Our results suggested that rs12041331 genetic polymorphism was not an important contributor to clinical events in AMIS and TIA patients in the setting of secondary prevention.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> Our data do provide robust evidence that genetic variation in PEAR1 rs12041331 do not contribute to atherothrombotic or bleeding risk in minor stroke and TIA patients treated with DAPT.<\/jats:p>","DOI":"10.3389\/fneur.2021.649056","type":"journal-article","created":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T07:54:43Z","timestamp":1622188483000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Impact of Platelet Endothelial Aggregation Receptor-1 Genotypes on Long-Term Cerebrovascular Outcomes in Patients With Minor Stroke or Transient Ischemic Attack"],"prefix":"10.3389","volume":"12","author":[{"given":"Xiao-Guang","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing-Yu","family":"Gu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang-Qiang","family":"Fu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shi-Wu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Xue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shan-Shan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Ming","family":"Kong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"You-Mei","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun-Hua","family":"Yue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1533","DOI":"10.1056\/NEJMoa1412981","article-title":"One-year risk of stroke after transient ischemic attack or minor stroke","volume":"374","author":"Amarenco","year":"2016","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1056\/NEJMoa1215340","article-title":"Clopidogrel with aspirin in acute minor stroke or transient ischemic attack","volume":"369","author":"Wang","year":"2013","journal-title":"N Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e344","DOI":"10.1161\/STR.0000000000000211","article-title":"Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association\/American Stroke Association","volume":"50","author":"Powers","year":"2019","journal-title":"Stroke"},{"key":"B4","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1111\/j.1747-4949.2012.00929.x","article-title":"Aspirin resistance in Chinese stroke patients increased the rate of recurrent stroke and other vascular events","volume":"8","author":"Yi","year":"2013","journal-title":"Int J Stroke"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1222","DOI":"10.1016\/j.jstrokecerebrovasdis.2016.02.013","article-title":"Clopidogrel resistance increases rate of recurrent stroke and other vascular events in Chinese population","volume":"25","author":"Yi","year":"2016","journal-title":"J Stroke Cerebrovasc Dis"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1399-0004.2008.01105.x","article-title":"The genetics of antiplatelet drug resistance","volume":"75","author":"Feher","year":"2009","journal-title":"Clin Genet"},{"key":"B7","doi-asserted-by":"publisher","first-page":"24680","DOI":"10.1074\/jbc.M413411200","article-title":"Platelet endothelial aggregation receptor 1 (PEAR1), a novel epidermal growth factor repeat-containing transmembrane receptor, participates in platelet contact-induced activation","volume":"280","author":"Nanda","year":"2005","journal-title":"J Biol Chem"},{"key":"B8","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1038\/ng.604","article-title":"Genome-wide meta-analyses identifies seven loci associated with platelet aggregation in response to agonists","volume":"42","author":"Johnson","year":"2010","journal-title":"Nat Genet"},{"key":"B9","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/s12863-015-0217-9","article-title":"Genome-wide association study of platelet aggregation in African Americans","volume":"16","author":"Qayyum","year":"2015","journal-title":"BMC Genet"},{"key":"B10","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1080\/09537104.2018.1447659","article-title":"Targeted deep sequencing of the PEAR1 locus for platelet aggregation in European and African American families","volume":"30","author":"Keramati","year":"2019","journal-title":"Platelets"},{"key":"B11","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1093\/ehjcvp\/pvz045","article-title":"Pharmacogenomic polygenic response score predicts ischaemic events and cardiovascular mortality in clopidogrel-treated patients","volume":"6","author":"Lewis","year":"2020","journal-title":"Eur Heart J Cardiovasc Pharmacother"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1182\/blood-2015-11-682153","article-title":"Allele-specific DNA methylation reinforces PEAR1 enhancer activity","volume":"128","author":"Izzi","year":"2016","journal-title":"Blood"},{"key":"B13","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1186\/s13148-019-0744-8","article-title":"Variation of PEAR1 DNA methylation influences platelet and leukocyte function","volume":"11","author":"Izzi","year":"2019","journal-title":"Clin Epigenetics"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1002\/cpt.1959","article-title":"Genetic variation in PEAR1, cardiovascular outcomes and effects of aspirin in a healthy elderly population","volume":"108","author":"Lewis","year":"2020","journal-title":"Clin Pharmacol Ther"},{"key":"B15","doi-asserted-by":"publisher","first-page":"e007019","DOI":"10.1161\/CIRCINTERVENTIONS.118.007019","article-title":"Impact of platelet endothelial aggregation receptor-1 genotypes on platelet reactivity and early cardiovascular outcomes in patients undergoing percutaneous coronary intervention and treated with aspirin and clopidogrel","volume":"12","author":"Xu","year":"2019","journal-title":"Circ Cardiovasc Interv"},{"key":"B16","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1186\/s12881-017-0411-x","article-title":"PEAR1 is not a major susceptibility gene for cardiovascular disease in a Flemish population","volume":"18","author":"Yang","year":"2017","journal-title":"BMC Med Genet"},{"key":"B17","doi-asserted-by":"publisher","first-page":"e16457","DOI":"10.1097\/MD.0000000000016457","article-title":"Effect of 106PEAR1 and 168PTGS1 genetic polymorphisms on recurrent ischemic stroke in Chinese patient","volume":"98","author":"Zhao","year":"2019","journal-title":"Medicine (Baltimore)"},{"key":"B18","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1111\/j.1538-7836.2009.03678.x","article-title":"Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients","volume":"8","author":"Schulman","year":"2010","journal-title":"J Thromb Haemost"},{"key":"B19","doi-asserted-by":"publisher","first-page":"3367","DOI":"10.1182\/blood-2010-11-320788","article-title":"Identification of a specific intronic PEAR1 gene variant associated with greater platelet aggregability and protein expression","volume":"118","author":"Faraday","year":"2011","journal-title":"Blood"},{"key":"B20","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1161\/CIRCGENETICS.111.964627","article-title":"Genetic variation in PEAR1 is associated with platelet aggregation and cardiovascular outcomes","volume":"6","author":"Lew5is","year":"2013","journal-title":"Circ Cardiovasc Genet"},{"key":"B21","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1097\/FPC.0000000000000349","article-title":"Pharmacogenetic and clinical predictors of response to clopidogrel plus aspirin after acute coronary syndrome in Egyptians","volume":"28","author":"Fathy","year":"2018","journal-title":"Pharmacogenet Genomics"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1038\/aps.2016.90","article-title":"Associations of MDR1, TBXA2R, PLA2G7, and PEAR1 genetic polymorphisms with the platelet activity in Chinese ischemic stroke patients receiving aspirin therapy","volume":"37","author":"Peng","year":"2016","journal-title":"Acta Pharmacol Sin"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.3390\/ijms19041069","article-title":"Cell-specific PEAR1 methylation studies reveal a locus that coordinates expression of multiple genes","volume":"19","author":"Izzi","year":"2018","journal-title":"Int J Mol Sci"},{"key":"B24","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1111\/cts.12438","article-title":"Prospective evaluation of genetic variation in platelet endothelial aggregation receptor 1 reveals aspirin-dependent effects on platelet aggregation pathways","volume":"10","author":"Backman","year":"2017","journal-title":"Clin Transl Sci"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2021.649056\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T13:52:19Z","timestamp":1622469139000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2021.649056\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,28]]},"references-count":24,"alternative-id":["10.3389\/fneur.2021.649056"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2021.649056","relation":{},"ISSN":["1664-2295"],"issn-type":[{"type":"electronic","value":"1664-2295"}],"subject":[],"published":{"date-parts":[[2021,5,28]]},"article-number":"649056"}}