{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T07:41:11Z","timestamp":1792136471697,"version":"4.4.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ATVB"],"published-print":{"date-parts":[[1998,4]]},"abstract":"<jats:p><jats:italic>Abstract<\/jats:italic>\u2014In an attempt to identify genetic factors underlying extreme alterations of serum HDL cholesterol (HDL-C) concentrations, we examined two probands with HDL-C levels &lt;0.2 mmol\/L and subsequently screened two large cohorts of smoking men, one with very low (0.2 to 0.7 mmol\/L, n=156) and the other with elevated (1.9 to 3.6 mmol\/L, n=160) HDL-C levels, for the newly detected mutations as well as some other mutations proposed to affect HDL-C levels. One of the probands had corneal opacities, microalbuminuria, hypertriglyceridemia, and reduced LDL apoprotein B concentration; the other had anemia and presented with stomatocytosis in his peripheral blood. The first proband was found to be homozygous for a novel LCAT Gly<jats:sup>230<\/jats:sup>Arg (LCAT<jats:sub>Fin<\/jats:sub>) mutation, and the second was homozygous for an Arg<jats:sup>399<\/jats:sup>Cys mutation we described previously. Transient expression of the mutant LCAT<jats:sub>Fin<\/jats:sub>cDNA in COS cells disclosed markedly diminished LCAT enzyme activity. In the low\u2013HDL-C group of men (n=156), 8 carriers of LCAT<jats:sub>Fin<\/jats:sub>and 1 carrier of the LCAT Arg<jats:sup>399<\/jats:sup>Cys were identified. In addition, the frequency of the lipoprotein lipase (LPL) Asn<jats:sup>291<\/jats:sup>Ser mutation was significantly (<jats:italic>P<\/jats:italic>&lt;.05) higher in the low\u2013HDL-C group (4.8%) than in the high\u2013HDL-C group (1.6%). In addition, we identified 1 carrier of the intron 14G\u2192A mutation of cholesterol ester transfer protein (CETP) in the high\u2013HDL-C group and subsequently demonstrated cosegregation of the mutant allele with elevated HDL-C levels in the proband\u2019s family. In conclusion, we have identified a novel LCAT gene Gly<jats:sup>230<\/jats:sup>Arg mutation (LCAT<jats:sub>Fin<\/jats:sub>), which, together with the LPL Asn<jats:sup>291<\/jats:sup>Ser mutation, represents a relatively common genetic cause of diminishing HDL-C levels, at least among Finns. This article also reports occurrence of a CETP mutation in subjects having non-Japanese roots.<\/jats:p>","DOI":"10.1161\/01.atv.18.4.591","type":"journal-article","created":{"date-parts":[[2011,6,17]],"date-time":"2011-06-17T19:44:19Z","timestamp":1308339859000},"page":"591-598","source":"Crossref","is-referenced-by-count":29,"title":["Molecular Genetic Study of Finns With Hypoalphalipoproteinemia and Hyperalphalipoproteinemia"],"prefix":"10.1161","volume":"18","author":[{"given":"H.E.","family":"Miettinen","sequence":"first","affiliation":[{"name":"From the Department of Medicine, University of Helsinki (H.E.M., H.G., T.A.M., K.K.); Orion Research, Orion Corp Biocenter, Helsinki (J.T.); National Public Health Institute, Helsinki (J.V., M.J., J.K.H.); and Department of Medicine, University of Turku (I.K.), Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Gylling","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, University of Helsinki (H.E.M., H.G., T.A.M., K.K.); Orion Research, Orion Corp Biocenter, Helsinki (J.T.); National Public Health Institute, Helsinki (J.V., M.J., J.K.H.); and Department of Medicine, University of Turku (I.K.), Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Tenhunen","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, University of Helsinki (H.E.M., H.G., T.A.M., K.K.); Orion Research, Orion Corp Biocenter, Helsinki (J.T.); National Public Health Institute, Helsinki (J.V., M.J., J.K.H.); and Department of Medicine, University of Turku (I.K.), Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Virtamo","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, University of Helsinki (H.E.M., H.G., T.A.M., K.K.); Orion Research, Orion Corp Biocenter, Helsinki (J.T.); National Public Health Institute, Helsinki (J.V., M.J., J.K.H.); and Department of Medicine, University of Turku (I.K.), Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Jauhiainen","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, University of Helsinki (H.E.M., H.G., T.A.M., K.K.); Orion Research, Orion Corp Biocenter, Helsinki (J.T.); National Public Health Institute, Helsinki (J.V., M.J., J.K.H.); and Department of Medicine, University of Turku (I.K.), Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.K.","family":"Huttunen","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, University of Helsinki (H.E.M., H.G., T.A.M., K.K.); Orion Research, Orion Corp Biocenter, Helsinki (J.T.); National Public Health Institute, Helsinki (J.V., M.J., J.K.H.); and Department of Medicine, University of Turku (I.K.), Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Kantola","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, University of Helsinki (H.E.M., H.G., T.A.M., K.K.); Orion Research, Orion Corp Biocenter, Helsinki (J.T.); National Public Health Institute, Helsinki (J.V., M.J., J.K.H.); and Department of Medicine, University of Turku (I.K.), Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.A.","family":"Miettinen","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, University of Helsinki (H.E.M., H.G., T.A.M., K.K.); Orion Research, Orion Corp Biocenter, Helsinki (J.T.); National Public Health Institute, Helsinki (J.V., M.J., J.K.H.); and Department of Medicine, University of Turku (I.K.), Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Kontula","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, University of Helsinki (H.E.M., H.G., T.A.M., K.K.); Orion Research, Orion Corp Biocenter, Helsinki (J.T.); National Public Health Institute, Helsinki (J.V., M.J., J.K.H.); and Department of Medicine, University of Turku (I.K.), Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198911093211907"},{"key":"e_1_3_2_2_2","unstructured":"Breslow JL. 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