{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T15:24:31Z","timestamp":1794324271833,"version":"4.9.0"},"reference-count":18,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JNS"],"published-print":{"date-parts":[[2016,6]]},"abstract":"\n OBJECT<\/jats:title>\n \n Symptomatic intracranial atherosclerotic disease (ICAD) has a high risk of recurrent stroke. Genetic polymorphisms in\n CYP2C19<\/jats:italic>\n and\n CES1<\/jats:italic>\n are associated with adverse outcomes in cardiovascular patients, but have not been studied in ICAD. The authors studied\n CYP2C19<\/jats:italic>\n and\n CES1<\/jats:italic>\n single-nucleotide polymorphisms (SNPs) in symptomatic ICAD patients.\n <\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n \n Genotype testing for\n \n CYP2C19*2,\n *<\/jats:sup>\n 3,\n *<\/jats:sup>\n 8,\n *<\/jats:sup>\n 17\n <\/jats:italic>\n and\n CES1<\/jats:italic>\n G143E was performed on 188 adult symptomatic ICAD patients from 3 medical centers who were medically managed with clopidogrel and aspirin. Testing was performed prospectively at 1 center, and retrospectively from a DNA sample biorepository at 2 centers. Multiple logistic regression and Cox regression analysis were performed to assess the association of these SNPs with the primary endpoint, which was a composite of transient ischemic attack (TIA), stroke, myocardial infarction, or death within 12 months.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n The primary endpoint occurred in 14.9% of the 188 cases. In multiple logistic regression analysis, the presence of the\n CYP2C19<\/jats:italic>\n loss of function (LOF) alleles *2, *3, and\n *8<\/jats:italic>\n in the medically managed patients was associated with lower odds of primary endpoint compared with wild-type homozygotes (odds ratio [OR] 0.13, 95% CI 0.03\u20130.62, p = 0.0101). Cox regression analysis demonstrated the\n CYP2C19<\/jats:italic>\n LOF carriers had a lower risk for the primary endpoint, with hazard ratio (HR) of 0.27 (95% CI 0.08\u20130.95), p = 0.041. A sensitivity analysis of a secondary composite endpoint of TIA, stroke, or death demonstrated a significant trend in multiple logistic regression analysis of\n CYP2C19<\/jats:italic>\n variants, with lower odds of secondary endpoint in patients carrying at least 1 LOF allele\n (*2, *3, *8)<\/jats:italic>\n than in wild-type homozygotes (OR 0.27, 95% CI 0.06\u20131.16, p = 0.078). Cox regression analysis demonstrated that the carriers of\n CYP2C19<\/jats:italic>\n LOF alleles had a lower risk forthe secondary composite endpoint (HR 0.22, 95% CI 0.05\u20131.04, p = 0.056).\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS<\/jats:title>\n \n This is the first study examining genetic variants and their effects in symptomatic ICAD. Variant alleles of\n CYP2C19 (*2, *3, *8)<\/jats:italic>\n were associated with lower odds of the primary and secondary composite endpoints. However, the direction of the association was opposite of what is expected based on this SNP. This may reflect an incomplete understanding of this genetic variation and its effect in symptomatic ICAD and warrants further investigations.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3171\/2015.6.jns15795","type":"journal-article","created":{"date-parts":[[2015,11,20]],"date-time":"2015-11-20T10:00:05Z","timestamp":1448013605000},"page":"1746-1751","source":"Crossref","is-referenced-by-count":29,"title":["CYP2C19 and CES1 polymorphisms and efficacy of clopidogrel and aspirin dual antiplatelet therapy in patients with symptomatic intracranial atherosclerotic disease"],"prefix":"10.3171","volume":"124","author":[{"given":"Brian L.","family":"Hoh","sequence":"first","affiliation":[{"name":"Departments of Neurosurgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, Florida; and\u00a0"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitrin W.","family":"McDonough","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, Florida; and\u00a0"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael F.","family":"Waters","sequence":"additional","affiliation":[{"name":"Neurology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrienne J.","family":"Royster","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany O.","family":"Sheehan","sequence":"additional","affiliation":[{"name":"Neurology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Burkley","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, Florida; and\u00a0"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taimour Y.","family":"Langaee","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, Florida; and\u00a0"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Mocco","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott L.","family":"Zuckerman","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishit","family":"Mummareddy","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus L.","family":"Stephens","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christie","family":"Ingram","sequence":"additional","affiliation":[{"name":"Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian M.","family":"Shaffer","sequence":"additional","affiliation":[{"name":"Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua C.","family":"Denny","sequence":"additional","affiliation":[{"name":"Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murray H.","family":"Brilliant","sequence":"additional","affiliation":[{"name":"Center for Human Genetics Research and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terrie E.","family":"Kitchner","sequence":"additional","affiliation":[{"name":"Center for Human Genetics Research and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James G.","family":"Linneman","sequence":"additional","affiliation":[{"name":"Biomedical Informatics Research Center, Marshfield Clinic Research Foundation, Marshfield, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan M.","family":"Roden","sequence":"additional","affiliation":[{"name":"Medicine, and"},{"name":"Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, Florida; and\u00a0"},{"name":"Division of Cardiovascular Medicine, College of Medicine, 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