{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:34:58Z","timestamp":1753889698898,"version":"3.41.2"},"reference-count":23,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"16","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,8,16]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Insulin receptor substrate\u20101 (\n              <jats:italic>IRS\u20101<\/jats:italic>\n              ) rs956115 is associated with vascular risk in patients with coronary artery disease and concomitant diabetes.\n              <jats:italic>CYP2C19*2<\/jats:italic>\n              (rs4244285) modulates clopidogrel response and predicts the outcome of coronary artery disease. This study was designed to explore the association between\n              <jats:italic>IRS\u20101<\/jats:italic>\n              ,\n              <jats:italic>CYP2C19*2<\/jats:italic>\n              genotypes, platelet reactivity, and 1\u2010year outcome in patients with coronary artery disease undergoing percutaneous coronary intervention.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Genotyping was performed using an improved multiplex ligation detection reaction technique. Platelet aggregation was assessed by light transmission aggregometry. Major adverse cardiovascular events were defined as a composite of cardiovascular death, myocardial infarction, and ischemic stroke. A total of 2213 consecutive patients were screened and 1614 were recruited. At 1\u00a0month, patients with\n              <jats:italic>IRS\u20101<\/jats:italic>\n              CG genotype had significantly lower levels of ADP\u2010induced platelet aggregation compared with patients with CC homozygotes. Patients with\n              <jats:italic>IRS\u20101<\/jats:italic>\n              CG or GG genotype had a 2.09\u2010fold higher risk of major adverse cardiovascular events compared with those with CC homozygotes (95% CI, 1.04\u20134.19;\n              <jats:italic>P<\/jats:italic>\n              =0.0376). By comparison, patients with\n              <jats:italic>CYP2C19*2<\/jats:italic>\n              GA or AA genotype had higher ADP\u2010induced platelet aggregation compared with patients with GG homozygotes. Although there was no significant difference in risk of major adverse cardiovascular events between patients with GA\/AA and GG genotypes, patients with GA genotype had a 2.19\u2010fold higher risk than those with GG homozygotes (95% CI, 1.13\u20134.24;\n              <jats:italic>P<\/jats:italic>\n              =0.0200). No interaction between\n              <jats:italic>IRS\u20101<\/jats:italic>\n              and\n              <jats:italic>CYP2C19*2<\/jats:italic>\n              genotypes was observed.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              In patients following percutaneous coronary intervention,\n              <jats:italic>IRS\u20101<\/jats:italic>\n              GG\/CG and\n              <jats:italic>CYP2C19*2<\/jats:italic>\n              GA genotypes were associated with 2.09\u2010 and 2.19\u2010fold increased cardiovascular risk, respectively, at 1\u2010year follow\u2010up. The association between\n              <jats:italic>IRS\u20101<\/jats:italic>\n              genotypes and major adverse cardiovascular events appeared to be independent of known clinical predictors.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Registration<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              ; Unique identifier: NCT01968499.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.121.025058","type":"journal-article","created":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T09:15:08Z","timestamp":1659690908000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Impact of Insulin Receptor Substrate\u20101 rs956115 and CYP2C19 rs4244285 Genotypes on Clinical Outcome of Patients Undergoing Percutaneous Coronary Intervention"],"prefix":"10.1161","volume":"11","author":[{"given":"Jiaxin","family":"Zong","sequence":"first","affiliation":[{"name":"Departments of Cardiology The First Affiliated Hospital of Nanjing Medical University Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingdan","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics School of Public Health Nanjing Medical University Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tong","family":"Wang","sequence":"additional","affiliation":[{"name":"Departments of Cardiology The First Affiliated Hospital of Nanjing Medical University Nanjing Jiangsu China"},{"name":"Department of Cardiology The First People\u2019s Hospital of Yancheng Yancheng Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3031-3860","authenticated-orcid":false,"given":"Inam","family":"Ullah","sequence":"additional","affiliation":[{"name":"Departments of Cardiology The First Affiliated Hospital of Nanjing Medical University Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke","family":"Xu","sequence":"additional","affiliation":[{"name":"Departments of Cardiology The First Affiliated Hospital of Nanjing Medical University Nanjing Jiangsu China"},{"name":"Department of Cardiology Shanghai Chest HospitalShanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Departments of Cardiology The First Affiliated Hospital of Nanjing Medical University Nanjing Jiangsu 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