title: Lipoprotein subfractions highly associated with renal damage in familial lecithin:cholesterol acyltransferase deficiency.
abstract: OBJECTIVE
  In familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD), deposition of abnormal lipoproteins in the renal stroma ultimately leads to renal failure. However, fish-eye disease (FED) does not lead to renal damage although the causative mutations for both FLD and FED lie within the same LCAT gene. This study was performed to identify the lipoproteins important for the development of renal failure in genetically diagnosed FLD in comparison with FED, using high-performance liquid chromatography with a gel filtration column.
  
  
  RESULTS
  Lipoprotein profiles of 9 patients with LCAT deficiency were examined. Four lipoprotein fractions specific to both FLD and FED were identified: (1) large lipoproteins (>80 nm), (2) lipoproteins corresponding to large low-density lipoprotein (LDL), (3) lipoproteins corresponding to small LDL to large high-density lipoprotein, and (4) to small high-density lipoprotein. Contents of cholesteryl ester and triglyceride of the large LDL in FLD (below detection limit and 45.8±3.8%) and FED (20.7±6.4% and 28.0±6.5%) were significantly different, respectively. On in vitro incubation with recombinant LCAT, content of cholesteryl ester in the large LDL in FLD, but not in FED, was significantly increased (to 4.2±1.4%), whereas dysfunctional high-density lipoprotein was diminished in both FLD and FED.
  
  
  CONCLUSIONS
  Our novel analytic approach using high-performance liquid chromatography with a gel filtration column identified large LDL and high-density lipoprotein with a composition specific to FLD, but not to FED. The abnormal lipoproteins were sensitive to treatment with recombinant LCAT and thus may play a causal role in the renal pathology of FLD.
authors.affiliation: From the Department of Genome Research and Clinical Application, Graduate School of Medicine (M.K., S.A., Y.A., H.B.) and Center for Advanced Medicine, Chiba University Hospital (M.K.), Chiba University, Chiba, Japan; Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (A.G.H., E.S.G.S.); Department of Nephrology in Internal Medicine, Kitasato University Hospital, Sagamihara, Japan (K.K.); Department of Internal Medicine and Molecular Science, Osaka University Graduate School of Medicine, Suita, Japan (S.Y.); Division of Endocrinology and Metabolism, Department of Medicine, Diabetes Center, Jichi Medical University, Shimotsuke, Japan (S.I.); Chiba University, Chiba, Japan (Y.S.); and Department of Clinical-Laboratory and Experimental-Research Medicine, Toho University Sakura Medical Center, Sakura, Japan (H.B.).
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kuroda
authors.affiliation: From the Department of Genome Research and Clinical Application, Graduate School of Medicine (M.K., S.A., Y.A., H.B.) and Center for Advanced Medicine, Chiba University Hospital (M.K.), Chiba University, Chiba, Japan; Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (A.G.H., E.S.G.S.); Department of Nephrology in Internal Medicine, Kitasato University Hospital, Sagamihara, Japan (K.K.); Department of Internal Medicine and Molecular Science, Osaka University Graduate School of Medicine, Suita, Japan (S.Y.); Division of Endocrinology and Metabolism, Department of Medicine, Diabetes Center, Jichi Medical University, Shimotsuke, Japan (S.I.); Chiba University, Chiba, Japan (Y.S.); and Department of Clinical-Laboratory and Experimental-Research Medicine, Toho University Sakura Medical Center, Sakura, Japan (H.B.).
authors.forename: Adriaan G
authors.initials: AG
authors.lastname: Holleboom
authors.affiliation: From the Department of Genome Research and Clinical Application, Graduate School of Medicine (M.K., S.A., Y.A., H.B.) and Center for Advanced Medicine, Chiba University Hospital (M.K.), Chiba University, Chiba, Japan; Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (A.G.H., E.S.G.S.); Department of Nephrology in Internal Medicine, Kitasato University Hospital, Sagamihara, Japan (K.K.); Department of Internal Medicine and Molecular Science, Osaka University Graduate School of Medicine, Suita, Japan (S.Y.); Division of Endocrinology and Metabolism, Department of Medicine, Diabetes Center, Jichi Medical University, Shimotsuke, Japan (S.I.); Chiba University, Chiba, Japan (Y.S.); and Department of Clinical-Laboratory and Experimental-Research Medicine, Toho University Sakura Medical Center, Sakura, Japan (H.B.).
authors.forename: Erik S G
authors.initials: ES
authors.lastname: Stroes
authors.affiliation: From the Department of Genome Research and Clinical Application, Graduate School of Medicine (M.K., S.A., Y.A., H.B.) and Center for Advanced Medicine, Chiba University Hospital (M.K.), Chiba University, Chiba, Japan; Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (A.G.H., E.S.G.S.); Department of Nephrology in Internal Medicine, Kitasato University Hospital, Sagamihara, Japan (K.K.); Department of Internal Medicine and Molecular Science, Osaka University Graduate School of Medicine, Suita, Japan (S.Y.); Division of Endocrinology and Metabolism, Department of Medicine, Diabetes Center, Jichi Medical University, Shimotsuke, Japan (S.I.); Chiba University, Chiba, Japan (Y.S.); and Department of Clinical-Laboratory and Experimental-Research Medicine, Toho University Sakura Medical Center, Sakura, Japan (H.B.).
authors.forename: Sakiyo
authors.initials: S
authors.lastname: Asada
authors.affiliation: From the Department of Genome Research and Clinical Application, Graduate School of Medicine (M.K., S.A., Y.A., H.B.) and Center for Advanced Medicine, Chiba University Hospital (M.K.), Chiba University, Chiba, Japan; Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (A.G.H., E.S.G.S.); Department of Nephrology in Internal Medicine, Kitasato University Hospital, Sagamihara, Japan (K.K.); Department of Internal Medicine and Molecular Science, Osaka University Graduate School of Medicine, Suita, Japan (S.Y.); Division of Endocrinology and Metabolism, Department of Medicine, Diabetes Center, Jichi Medical University, Shimotsuke, Japan (S.I.); Chiba University, Chiba, Japan (Y.S.); and Department of Clinical-Laboratory and Experimental-Research Medicine, Toho University Sakura Medical Center, Sakura, Japan (H.B.).
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Aoyagi
authors.affiliation: From the Department of Genome Research and Clinical Application, Graduate School of Medicine (M.K., S.A., Y.A., H.B.) and Center for Advanced Medicine, Chiba University Hospital (M.K.), Chiba University, Chiba, Japan; Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (A.G.H., E.S.G.S.); Department of Nephrology in Internal Medicine, Kitasato University Hospital, Sagamihara, Japan (K.K.); Department of Internal Medicine and Molecular Science, Osaka University Graduate School of Medicine, Suita, Japan (S.Y.); Division of Endocrinology and Metabolism, Department of Medicine, Diabetes Center, Jichi Medical University, Shimotsuke, Japan (S.I.); Chiba University, Chiba, Japan (Y.S.); and Department of Clinical-Laboratory and Experimental-Research Medicine, Toho University Sakura Medical Center, Sakura, Japan (H.B.).
authors.forename: Kouju
authors.initials: K
authors.lastname: Kamata
authors.affiliation: From the Department of Genome Research and Clinical Application, Graduate School of Medicine (M.K., S.A., Y.A., H.B.) and Center for Advanced Medicine, Chiba University Hospital (M.K.), Chiba University, Chiba, Japan; Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (A.G.H., E.S.G.S.); Department of Nephrology in Internal Medicine, Kitasato University Hospital, Sagamihara, Japan (K.K.); Department of Internal Medicine and Molecular Science, Osaka University Graduate School of Medicine, Suita, Japan (S.Y.); Division of Endocrinology and Metabolism, Department of Medicine, Diabetes Center, Jichi Medical University, Shimotsuke, Japan (S.I.); Chiba University, Chiba, Japan (Y.S.); and Department of Clinical-Laboratory and Experimental-Research Medicine, Toho University Sakura Medical Center, Sakura, Japan (H.B.).
authors.forename: Shizuya
authors.initials: S
authors.lastname: Yamashita
authors.affiliation: From the Department of Genome Research and Clinical Application, Graduate School of Medicine (M.K., S.A., Y.A., H.B.) and Center for Advanced Medicine, Chiba University Hospital (M.K.), Chiba University, Chiba, Japan; Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (A.G.H., E.S.G.S.); Department of Nephrology in Internal Medicine, Kitasato University Hospital, Sagamihara, Japan (K.K.); Department of Internal Medicine and Molecular Science, Osaka University Graduate School of Medicine, Suita, Japan (S.Y.); Division of Endocrinology and Metabolism, Department of Medicine, Diabetes Center, Jichi Medical University, Shimotsuke, Japan (S.I.); Chiba University, Chiba, Japan (Y.S.); and Department of Clinical-Laboratory and Experimental-Research Medicine, Toho University Sakura Medical Center, Sakura, Japan (H.B.).
authors.forename: Shun
authors.initials: S
authors.lastname: Ishibashi
authors.affiliation: From the Department of Genome Research and Clinical Application, Graduate School of Medicine (M.K., S.A., Y.A., H.B.) and Center for Advanced Medicine, Chiba University Hospital (M.K.), Chiba University, Chiba, Japan; Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (A.G.H., E.S.G.S.); Department of Nephrology in Internal Medicine, Kitasato University Hospital, Sagamihara, Japan (K.K.); Department of Internal Medicine and Molecular Science, Osaka University Graduate School of Medicine, Suita, Japan (S.Y.); Division of Endocrinology and Metabolism, Department of Medicine, Diabetes Center, Jichi Medical University, Shimotsuke, Japan (S.I.); Chiba University, Chiba, Japan (Y.S.); and Department of Clinical-Laboratory and Experimental-Research Medicine, Toho University Sakura Medical Center, Sakura, Japan (H.B.).
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saito
authors.affiliation: From the Department of Genome Research and Clinical Application, Graduate School of Medicine (M.K., S.A., Y.A., H.B.) and Center for Advanced Medicine, Chiba University Hospital (M.K.), Chiba University, Chiba, Japan; Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (A.G.H., E.S.G.S.); Department of Nephrology in Internal Medicine, Kitasato University Hospital, Sagamihara, Japan (K.K.); Department of Internal Medicine and Molecular Science, Osaka University Graduate School of Medicine, Suita, Japan (S.Y.); Division of Endocrinology and Metabolism, Department of Medicine, Diabetes Center, Jichi Medical University, Shimotsuke, Japan (S.I.); Chiba University, Chiba, Japan (Y.S.); and Department of Clinical-Laboratory and Experimental-Research Medicine, Toho University Sakura Medical Center, Sakura, Japan (H.B.). hideaki.bujo@med.toho-u.ac.jp.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Bujo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D056947:Enzyme Replacement Therapy; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007668:Kidney / Q000473:pathology; D007863:Lecithin Cholesterol Acyltransferase Deficiency / Q000097:blood / Q000150:complications* / Q000188:drug therapy / Q000235:genetics; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000235:genetics / Q000627:therapeutic use; D011507:Proteinuria / Q000097:blood / Q000209:etiology; D011994:Recombinant Proteins / Q000627:therapeutic use; D051437:Renal Insufficiency / Q000097:blood / Q000209:etiology* / Q000235:genetics / Q000473:pathology
chemical_list: D015415:Biomarkers; D008074:Lipoproteins; D011994:Recombinant Proteins; D007862:Phosphatidylcholine-Sterol O-Acyltransferase
keywords: LDL; chromatography, gel; lecithin acyltransferase deficiency; renal insufficiency