{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:26:09Z","timestamp":1790015169437,"version":"4.0.1"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"21","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,11,2]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Translocation of lipopolysaccharide from gram\u2010negative bacteria into the systemic circulation results in endotoxemia. In addition to acute infections, endotoxemia is detected in cardiometabolic disorders, such as cardiovascular diseases and obesity.<\/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              We performed a genome\u2010wide association study of serum lipopolysaccharide activity in 11\u00a0296 individuals from 6 different Finnish study cohorts. Endotoxemia was measured by limulus amebocyte lysate assay in the whole population and by 2 other techniques (Endolisa and high\u2010performance liquid chromatography\/tandem mass spectrometry) in subpopulations. The associations of the composed genetic risk score of endotoxemia and thrombosis\u2010related clinical end points for 195\u00a0170 participants were analyzed in FinnGen. Lipopolysaccharide activity had a genome\u2010wide significant association with 741 single\u2010nucleotide polymorphisms in 5 independent loci, which were mainly located at genes affecting the contact activation of the coagulation cascade and lipoprotein metabolism and explained 1.5% to 9.2% of the variability in lipopolysaccharide activity levels. The closest genes included\n              <jats:italic>KNG1<\/jats:italic>\n              ,\n              <jats:italic>KLKB1<\/jats:italic>\n              ,\n              <jats:italic>F12<\/jats:italic>\n              ,\n              <jats:italic>SLC34A1<\/jats:italic>\n              ,\n              <jats:italic>YPEL4<\/jats:italic>\n              ,\n              <jats:italic>CLP1<\/jats:italic>\n              ,\n              <jats:italic>ZDHHC5<\/jats:italic>\n              ,\n              <jats:italic>SERPING1<\/jats:italic>\n              ,\n              <jats:italic>CBX5<\/jats:italic>\n              , and\n              <jats:italic>LIPC<\/jats:italic>\n              . The genetic risk score of endotoxemia was associated with deep vein thrombosis, pulmonary embolism, pulmonary heart disease, and venous thromboembolism.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">The biological activity of lipopolysaccharide in the circulation (ie, endotoxemia) has a small but highly significant genetic component. Endotoxemia is associated with genetic variation in the contact activation pathway, vasoactivity, and lipoprotein metabolism, which play important roles in host defense, lipopolysaccharide neutralization, and thrombosis, and thereby thromboembolism and stroke.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.121.022482","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T14:24:06Z","timestamp":1634739846000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":25,"title":["Genetic Profile of Endotoxemia Reveals an Association With Thromboembolism and Stroke"],"prefix":"10.1161","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9670-339X","authenticated-orcid":false,"given":"Jaakko","family":"Leskel\u00e4","sequence":"first","affiliation":[{"name":"Oral and Maxillofacial Diseases University of Helsinki and Helsinki University Hospital Helsinki 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