{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T17:32:16Z","timestamp":1791048736411,"version":"4.1.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"17","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2009,10,27]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Background\u2014<\/jats:italic>\n            <\/jats:bold>\n            In congenital long-QT syndrome (LQTS), a genetically heterogeneous disorder that predisposes to sudden cardiac death, genetic factors other than the primary mutation may modify the probability of life-threatening events. Recent evidence indicates that common variants in\n            <jats:italic>NOS1AP<\/jats:italic>\n            are associated with the QT-interval duration in the general population.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            We tested the hypothesis that common variants in\n            <jats:italic>NOS1AP<\/jats:italic>\n            modify the risk of clinical manifestations and the degree of QT-interval prolongation in a South African LQTS population (500 subjects, 205 mutation carriers) segregating a founder mutation in\n            <jats:italic>KCNQ1<\/jats:italic>\n            (A341V) using a family-based association analysis.\n            <jats:italic>NOS1AP<\/jats:italic>\n            variants were significantly associated with the occurrence of symptoms (rs4657139,\n            <jats:italic>P<\/jats:italic>\n            =0.019; rs16847548,\n            <jats:italic>P<\/jats:italic>\n            =0.003), with clinical severity, as manifested by a greater probability for cardiac arrest and sudden death (rs4657139,\n            <jats:italic>P<\/jats:italic>\n            =0.028; rs16847548,\n            <jats:italic>P<\/jats:italic>\n            =0.014), and with greater likelihood of having a QT interval in the top 40% of values among all mutation carriers (rs4657139,\n            <jats:italic>P<\/jats:italic>\n            =0.03; rs16847548,\n            <jats:italic>P<\/jats:italic>\n            =0.03).\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            These findings indicate that\n            <jats:italic>NOS1AP<\/jats:italic>\n            , a gene first identified as affecting the QTc interval in a general population, also influences sudden death risk in subjects with LQTS. The association of\n            <jats:italic>NOS1AP<\/jats:italic>\n            genetic variants with risk for life-threatening arrhythmias suggests that this gene is a genetic modifier of LQTS, and this knowledge may be clinically useful for risk stratification for patients with this disease, after validation in other LQTS populations.\n          <\/jats:p>","DOI":"10.1161\/circulationaha.109.879643","type":"journal-article","created":{"date-parts":[[2009,10,13]],"date-time":"2009-10-13T01:54:26Z","timestamp":1255398866000},"page":"1657-1663","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":248,"title":["<i>NOS1AP<\/i>\n            Is a Genetic Modifier of the Long-QT Syndrome"],"prefix":"10.1161","volume":"120","author":[{"given":"Lia","family":"Crotti","sequence":"first","affiliation":[{"name":"From the Section of Cardiology, Department of Lung, Blood, and Heart (L.C., P.J.S.), and Department of Heath Sciences (M.C.M.), University of Pavia, Pavia, Italy; Department of Cardiology (L.C., P.J.S.) and Molecular Cardiology Laboratory (L.C., R.I., P.J.S.), IRCCS Fondazione Policlinico San Matteo, Pavia, Italy; Division of Statistical Genetics, Department of Biostatistics, Mailman School of Public Health, and Psychiatry Department, Columbia University Medical Center, New York, NY (M.C.M., D.A.G...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Monti","sequence":"additional","affiliation":[{"name":"From the Section of Cardiology, Department of Lung, Blood, and Heart (L.C., P.J.S.), and Department of Heath Sciences (M.C.M.), University of Pavia, Pavia, Italy; Department of Cardiology (L.C., P.J.S.) and Molecular Cardiology Laboratory (L.C., R.I., P.J.S.), IRCCS Fondazione Policlinico San Matteo, Pavia, Italy; Division of Statistical Genetics, Department of Biostatistics, Mailman School of Public Health, and Psychiatry Department, Columbia University Medical Center, New York, NY (M.C.M., D.A.G...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Insolia","sequence":"additional","affiliation":[{"name":"From the Section of Cardiology, Department of Lung, Blood, and Heart (L.C., P.J.S.), and Department of Heath Sciences (M.C.M.), University of Pavia, Pavia, Italy; Department of Cardiology (L.C., P.J.S.) and Molecular Cardiology Laboratory (L.C., R.I., P.J.S.), IRCCS Fondazione Policlinico San Matteo, Pavia, Italy; Division of Statistical Genetics, Department of Biostatistics, Mailman School of Public Health, and Psychiatry Department, Columbia University Medical Center, New York, NY (M.C.M., D.A.G...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Peljto","sequence":"additional","affiliation":[{"name":"From the Section of Cardiology, Department of Lung, Blood, and Heart (L.C., P.J.S.), and Department of Heath Sciences (M.C.M.), University of Pavia, Pavia, Italy; Department of Cardiology (L.C., P.J.S.) and Molecular Cardiology Laboratory (L.C., R.I., P.J.S.), IRCCS Fondazione Policlinico San Matteo, Pavia, Italy; Division of Statistical Genetics, Department of Biostatistics, Mailman School of Public Health, and Psychiatry Department, Columbia University Medical Center, New York, NY (M.C.M., D.A.G...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Althea","family":"Goosen","sequence":"additional","affiliation":[{"name":"From the Section of Cardiology, Department of Lung, Blood, and Heart (L.C., P.J.S.), and Department of Heath Sciences (M.C.M.), University of Pavia, Pavia, Italy; Department of Cardiology (L.C., P.J.S.) and Molecular Cardiology Laboratory (L.C., R.I., P.J.S.), IRCCS Fondazione Policlinico San Matteo, Pavia, Italy; Division of Statistical Genetics, Department of Biostatistics, Mailman School of Public Health, and Psychiatry Department, Columbia University Medical Center, New York, NY (M.C.M., D.A.G...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"Brink","sequence":"additional","affiliation":[{"name":"From the Section of Cardiology, Department of Lung, Blood, and Heart (L.C., P.J.S.), and Department of Heath Sciences (M.C.M.), University of Pavia, Pavia, Italy; Department of Cardiology (L.C., P.J.S.) and Molecular Cardiology Laboratory (L.C., R.I., P.J.S.), IRCCS Fondazione Policlinico San Matteo, Pavia, Italy; Division of Statistical Genetics, Department of Biostatistics, Mailman School of Public Health, and Psychiatry Department, Columbia University Medical Center, New York, NY (M.C.M., D.A.G...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Greenberg","sequence":"additional","affiliation":[{"name":"From the Section of Cardiology, Department of Lung, Blood, and Heart (L.C., P.J.S.), and Department of Heath Sciences (M.C.M.), University of Pavia, Pavia, Italy; Department of Cardiology (L.C., P.J.S.) and Molecular Cardiology Laboratory (L.C., R.I., P.J.S.), IRCCS Fondazione Policlinico San Matteo, Pavia, Italy; Division of Statistical Genetics, Department of Biostatistics, Mailman School of Public Health, and Psychiatry Department, Columbia University Medical Center, New York, NY (M.C.M., D.A.G...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"From the Section of Cardiology, Department of Lung, Blood, and Heart (L.C., P.J.S.), and Department of Heath Sciences (M.C.M.), University of Pavia, Pavia, Italy; Department of Cardiology (L.C., P.J.S.) and Molecular Cardiology Laboratory (L.C., R.I., P.J.S.), IRCCS Fondazione Policlinico San Matteo, Pavia, Italy; Division of Statistical Genetics, Department of Biostatistics, Mailman School of Public Health, and Psychiatry Department, Columbia University Medical Center, New York, NY (M.C.M., D.A.G...."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Alfred L.","family":"George","sequence":"additional","affiliation":[{"name":"From the Section of Cardiology, Department of Lung, Blood, and Heart (L.C., P.J.S.), and Department of Heath Sciences (M.C.M.), University of Pavia, Pavia, Italy; Department of Cardiology (L.C., P.J.S.) and Molecular Cardiology Laboratory (L.C., R.I., P.J.S.), IRCCS Fondazione Policlinico San Matteo, Pavia, Italy; Division of Statistical Genetics, Department of Biostatistics, Mailman School of Public Health, and Psychiatry Department, Columbia University Medical Center, New York, NY (M.C.M., D.A.G...."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","unstructured":"Schwartz PJ Crotti L. 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