{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:22:59Z","timestamp":1790266979653,"version":"4.1.0"},"reference-count":64,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ATVB"],"published-print":{"date-parts":[[1999,11]]},"abstract":"<jats:p>\n            <jats:italic>Abstract<\/jats:italic>\n            \u2014More than 90% of patients with type III hyperlipoproteinemia are homozygous carriers of the apolipoprotein (apo) E*2 allele. The great majority of these apoE2(Arg158\u2192Cys) homozygotes in the general population, however, are normolipidemic. Apparently, expression of the hyperlipidemic state requires additional genetic and\/or environmental factors, suggesting a multifactorial etiology. To elucidate these additional risk factors, we analyzed normolipidemic and hyperlipidemic apoE2 homozygotes. Hyperinsulinemia was observed in 27 of 49 apoE2 homozygotes and associated with elevated lipid levels: hyperinsulinemic apoE2 homozygotes had type III hyperlipoproteinemia 6 times more often than apoE2 homozygotes with normal insulin levels (odds ratio 6.2,\n            <jats:italic>P<\/jats:italic>\n            =0.02). We screened the normolipidemic and hyperlipidemic apoE2 homozygotes for common variants in candidate genes involved in lipolysis\u2014the APOA1-C3-A4 gene cluster, lipoprotein lipase, and hepatic lipase\u2014and analyzed for associations with the expression of hyperlipidemia. In the hyperinsulinemic group, the 7 carriers of the\n            <jats:italic>Sst<\/jats:italic>\n            I polymorphism (S2) in the APOC3 gene displayed severely elevated VLDL cholesterol (\n            <jats:italic>P<\/jats:italic>\n            <jats:sub>\n              insulin by\n              <jats:italic>Sst<\/jats:italic>\n              I\n            <\/jats:sub>\n            &lt;0.001) and VLDL triglyceride (\n            <jats:italic>P<\/jats:italic>\n            <jats:sub>\n              insulin by\n              <jats:italic>Sst<\/jats:italic>\n              I\n            <\/jats:sub>\n            &lt;0.01) and low levels of HDL (\n            <jats:italic>P<\/jats:italic>\n            <jats:sub>\n              insulin by\n              <jats:italic>Sst<\/jats:italic>\n              I\n            <\/jats:sub>\n            &lt;0.02). In the normoinsulinemic group, no such relation of the\n            <jats:italic>Sst<\/jats:italic>\n            I polymorphism with hyperlipidemia was observed. These data provide the first evidence for a combined effect of hyperinsulinemia and the\n            <jats:italic>Sst<\/jats:italic>\n            I polymorphism on the expression of hyperlipidemia in apoE2 homozygotes.\n          <\/jats:p>","DOI":"10.1161\/01.atv.19.11.2722","type":"journal-article","created":{"date-parts":[[2011,6,17]],"date-time":"2011-06-17T19:44:19Z","timestamp":1308339859000},"page":"2722-2729","source":"Crossref","is-referenced-by-count":27,"title":["Severe Hyperlipidemia in Apolipoprotein E2 Homozygotes Due to a Combined Effect of Hyperinsulinemia and an\n            <i>Sst<\/i>\n            I Polymorphism"],"prefix":"10.1161","volume":"19","author":[{"given":"Eric J. G.","family":"Sijbrands","sequence":"first","affiliation":[{"name":"From the Department of General Internal Medicine, Medical Faculty (E.J.G.S., A.E.M., A.H.M.S.), and the MGC\u2013Department of Human Genetics (M.J.V.H., R.R.F., P.D.K.), Leiden University Medical Center, and TNO-PG, Gaubius Laboratory (L.M.H.), Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u0308tte J. V.","family":"Hoffer","sequence":"additional","affiliation":[{"name":"From the Department of General Internal Medicine, Medical Faculty (E.J.G.S., A.E.M., A.H.M.S.), and the MGC\u2013Department of Human Genetics (M.J.V.H., R.R.F., P.D.K.), Leiden University Medical Center, and TNO-PG, Gaubius Laboratory (L.M.H.), Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Edo","family":"Meinders","sequence":"additional","affiliation":[{"name":"From the Department of General Internal Medicine, Medical Faculty (E.J.G.S., A.E.M., A.H.M.S.), and the MGC\u2013Department of Human Genetics (M.J.V.H., R.R.F., P.D.K.), Leiden University Medical Center, and TNO-PG, Gaubius Laboratory (L.M.H.), Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis M.","family":"Havekes","sequence":"additional","affiliation":[{"name":"From the Department of General Internal Medicine, Medical Faculty (E.J.G.S., A.E.M., A.H.M.S.), and the MGC\u2013Department of Human Genetics (M.J.V.H., R.R.F., P.D.K.), Leiden University Medical Center, and TNO-PG, Gaubius Laboratory (L.M.H.), Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rune R.","family":"Frants","sequence":"additional","affiliation":[{"name":"From the Department of General Internal Medicine, Medical Faculty (E.J.G.S., A.E.M., A.H.M.S.), and the MGC\u2013Department of Human Genetics (M.J.V.H., R.R.F., P.D.K.), Leiden University Medical Center, and TNO-PG, Gaubius Laboratory (L.M.H.), Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augustinus H. M.","family":"Smelt","sequence":"additional","affiliation":[{"name":"From the Department of General Internal Medicine, Medical Faculty (E.J.G.S., A.E.M., A.H.M.S.), and the MGC\u2013Department of Human Genetics (M.J.V.H., R.R.F., P.D.K.), Leiden University Medical Center, and TNO-PG, Gaubius Laboratory (L.M.H.), Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"De Knijff","sequence":"additional","affiliation":[{"name":"From the Department of General Internal Medicine, Medical Faculty (E.J.G.S., A.E.M., A.H.M.S.), and the MGC\u2013Department of Human Genetics (M.J.V.H., R.R.F., P.D.K.), Leiden University Medical Center, and TNO-PG, Gaubius Laboratory (L.M.H.), Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90346-E"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.1979.tb08069.x"},{"key":"e_1_3_2_3_2","unstructured":"Mahley RW Rall SC Jr. Type III hyperlipoproteinemia (dysbetalipoproteinemia): the role of apolipoprotein E in normal and abnormal lipoprotein metabolism. 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