{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:51:42Z","timestamp":1791348702420,"version":"4.3.1"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2007,11]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Objective\u2014<\/jats:italic>\n            <\/jats:bold>\n            The genetic determinants of severe hypertriglyceridemia (HTG; MIM 144650) in adults are poorly defined. We therefore resequenced 3 candidate genes, namely\n            <jats:italic>LPL<\/jats:italic>\n            ,\n            <jats:italic>APOC2<\/jats:italic>\n            , and\n            <jats:italic>APOA5<\/jats:italic>\n            , to search for accumulation of missense mutations in patients with severe HTG compared with normolipidemic subjects.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            We resequenced &gt;2 million base pairs of genomic DNA from 110 nondiabetic patients with severe HTG and determined the prevalence of coding sequence variants compared with 472 age- and sex-matched normolipidemic controls. We found: (1) heterozygous mutations (\n            <jats:italic>LPL<\/jats:italic>\n            p.Q-12E &gt;11X, p.D25H, p.W86R, p.G188E, p.I194T and p.P207L;\n            <jats:italic>APOC2<\/jats:italic>\n            p.K19T and IVS2\u201330G&gt;A) in 10.0% of severe HTG patients compared with 0.2% of controls (carrier odds ratio [OR] 52, 95% confidence interval [CI] 8.6 to 319); and (2) an association of the\n            <jats:italic>APOA5<\/jats:italic>\n            p.S19W missense variant with severe HTG (carrier OR 5.5 95% CI 3.3 to 9.1). Furthermore, either rare mutations or the\n            <jats:italic>APOA5<\/jats:italic>\n            p.S19W variant were found in 41.8% of HTG subjects compared with 8.9% of controls (carrier OR 7.4, 95% CI 4.5 to 12.0). Also, heterozygotes for rare mutations had a significantly reduced plasma triglyceride response to fibrate monotherapy.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            Both common and rare DNA variants in candidate genes were found in a substantial proportion of severe HTG patients. The findings underscore the value of candidate gene resequencing to understand the genetic contribution in complex lipoprotein and metabolic disorders.\n          <\/jats:p>","DOI":"10.1161\/atvbaha.107.150680","type":"journal-article","created":{"date-parts":[[2007,8,24]],"date-time":"2007-08-24T01:40:15Z","timestamp":1187919615000},"page":"2450-2455","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":101,"title":["Resequencing Genomic DNA of Patients With Severe Hypertriglyceridemia (MIM 144650)"],"prefix":"10.1161","volume":"27","author":[{"given":"Jian","family":"Wang","sequence":"first","affiliation":[{"name":"From the Vascular Biology Research Group (J.W., H.C., M.R.B., B.A.K., S.Z., R.L.P., R.A.H.), Robarts Research Institute and Schulich School of Medicine and Dentistry, London, Ontario, Canada; and Population Health Research Institute (S.A., S.Y.), McMaster University, Hamilton Health Sciences, Hamilton, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henian","family":"Cao","sequence":"additional","affiliation":[{"name":"From the Vascular Biology Research Group (J.W., H.C., M.R.B., B.A.K., S.Z., R.L.P., R.A.H.), Robarts Research Institute and Schulich School of Medicine and Dentistry, London, Ontario, Canada; and Population Health Research Institute (S.A., S.Y.), McMaster University, Hamilton Health Sciences, Hamilton, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R.","family":"Ban","sequence":"additional","affiliation":[{"name":"From the Vascular Biology Research Group (J.W., H.C., M.R.B., B.A.K., S.Z., R.L.P., R.A.H.), Robarts Research Institute and Schulich School of Medicine and Dentistry, London, Ontario, Canada; and Population Health Research Institute (S.A., S.Y.), McMaster University, Hamilton Health Sciences, Hamilton, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brooke A.","family":"Kennedy","sequence":"additional","affiliation":[{"name":"From the Vascular Biology Research Group (J.W., H.C., M.R.B., B.A.K., S.Z., R.L.P., R.A.H.), Robarts Research Institute and Schulich School of Medicine and Dentistry, London, Ontario, Canada; and Population Health Research Institute (S.A., S.Y.), McMaster University, Hamilton Health Sciences, Hamilton, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqi","family":"Zhu","sequence":"additional","affiliation":[{"name":"From the Vascular Biology Research Group (J.W., H.C., M.R.B., B.A.K., S.Z., R.L.P., R.A.H.), Robarts Research Institute and Schulich School of Medicine and Dentistry, London, Ontario, Canada; and Population Health Research Institute (S.A., S.Y.), McMaster University, Hamilton Health Sciences, Hamilton, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Anand","sequence":"additional","affiliation":[{"name":"From the Vascular Biology Research Group (J.W., H.C., M.R.B., B.A.K., S.Z., R.L.P., R.A.H.), Robarts Research Institute and Schulich School of Medicine and Dentistry, London, Ontario, Canada; and Population Health Research Institute (S.A., S.Y.), McMaster University, Hamilton Health Sciences, Hamilton, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salim","family":"Yusuf","sequence":"additional","affiliation":[{"name":"From the Vascular Biology Research Group (J.W., H.C., M.R.B., B.A.K., S.Z., R.L.P., R.A.H.), Robarts Research Institute and Schulich School of Medicine and Dentistry, London, Ontario, Canada; and Population Health Research Institute (S.A., S.Y.), McMaster University, Hamilton Health Sciences, Hamilton, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca L.","family":"Pollex","sequence":"additional","affiliation":[{"name":"From the Vascular Biology Research Group (J.W., H.C., M.R.B., B.A.K., S.Z., R.L.P., R.A.H.), Robarts Research Institute and Schulich School of Medicine and Dentistry, London, Ontario, Canada; 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