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Title: Characterization of five new mutants in the carboxyl-terminal domain of human apolipoprotein E: No cosegregation with severe hyperlipidemia

Abstract

Assessment of the apolipoprotein E (apoE) phenotype by isoelectric focusing of both hyperlipidemic and normolipidemic individuals identified five new variants. All mutations were confined to the downstream part of the APOE gene by using denaturing gradient gel electrophoresis (DGGE). Sequence analysis revealed five new mutations causing unique amino acid substitutions in the carboxyl-terminal part of the protein containing the putative lipid-binding domain. Three hyperlipoproteinemic probands were carriers of the APOE*2(Va1236[r arrow]Glu) allele, the APOE*3(Cys112-Arg; Arg251[r arrow]Gly) allele, or the APOE*1(Arg158[r arrow]Cys; Leu252[r arrow]Glu) allele. DGGE of the region encoding the receptor-binding domain was useful for haplotyping the mutations at codons 112 and 158. Family studies failed to demonstrate cosegregation between the new mutations and severe hyperlipoproteinemia, although a number of carriers for the APOE*3(Cys112[r arrow]Arg; Arg251[r arrow]Gly) allele and the APOE*1(Arg158-Cys; Leu252[r arrow]Glu) allele expressed hypertriglyceridemia and/ or hypercholesterolemia. Two other mutant alleles, APOE*4[sup [minus]] (Cys112[r arrow]Arg; Arg274[r arrow]His) and APOE*4[sup +] (Ser296[r arrow]Arg), were found in normolipidemic probands. The lack of cosegregation of these new mutations with severe hyperlipoproteinemia suggests that these mutations do not exert a dominant effect on the functioning of apoE. 41 refs., 5 figs., 1 tab.

Authors:
; ;  [1]; ; ; ; ; ;  [2]; ;  [3]
  1. Leiden Univ. (Netherlands)
  2. Univ. Hospital, Leiden (Netherlands)
  3. Westfalische Wilhelms-Universitaet, Muester (Germany)
Publication Date:
OSTI Identifier:
6220291
Resource Type:
Journal Article
Journal Name:
American Journal of Human Genetics; (United States)
Additional Journal Information:
Journal Volume: 52:5; Journal ID: ISSN 0002-9297
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; APOLIPOPROTEINS; GENE MUTATIONS; LIPIDS; METABOLIC DISEASES; LIPOPROTEINS; GENES; CHOLESTEROL; DNA SEQUENCING; TRIGLYCERIDES; DISEASES; ESTERS; HYDROXY COMPOUNDS; MUTATIONS; ORGANIC COMPOUNDS; PROTEINS; STEROIDS; STEROLS; STRUCTURAL CHEMICAL ANALYSIS; 550400* - Genetics; 550500 - Metabolism

Citation Formats

Maagdenberg, A.M.J.M. van den, Bruijn, I.H. de, Hofker, M H, Frants, R R, Knijff, P de, Smelt, A H.M., Leuven, J A.G., van't Hooft, F, Assmann, G, Havekes, L M, Weng, Wei, and Funke, H. Characterization of five new mutants in the carboxyl-terminal domain of human apolipoprotein E: No cosegregation with severe hyperlipidemia. United States: N. p., 1993. Web.
Maagdenberg, A.M.J.M. van den, Bruijn, I.H. de, Hofker, M H, Frants, R R, Knijff, P de, Smelt, A H.M., Leuven, J A.G., van't Hooft, F, Assmann, G, Havekes, L M, Weng, Wei, & Funke, H. Characterization of five new mutants in the carboxyl-terminal domain of human apolipoprotein E: No cosegregation with severe hyperlipidemia. United States.
Maagdenberg, A.M.J.M. van den, Bruijn, I.H. de, Hofker, M H, Frants, R R, Knijff, P de, Smelt, A H.M., Leuven, J A.G., van't Hooft, F, Assmann, G, Havekes, L M, Weng, Wei, and Funke, H. 1993. "Characterization of five new mutants in the carboxyl-terminal domain of human apolipoprotein E: No cosegregation with severe hyperlipidemia". United States.
@article{osti_6220291,
title = {Characterization of five new mutants in the carboxyl-terminal domain of human apolipoprotein E: No cosegregation with severe hyperlipidemia},
author = {Maagdenberg, A.M.J.M. van den and Bruijn, I.H. de and Hofker, M H and Frants, R R and Knijff, P de and Smelt, A H.M. and Leuven, J A.G. and van't Hooft, F and Assmann, G and Havekes, L M and Weng, Wei and Funke, H},
abstractNote = {Assessment of the apolipoprotein E (apoE) phenotype by isoelectric focusing of both hyperlipidemic and normolipidemic individuals identified five new variants. All mutations were confined to the downstream part of the APOE gene by using denaturing gradient gel electrophoresis (DGGE). Sequence analysis revealed five new mutations causing unique amino acid substitutions in the carboxyl-terminal part of the protein containing the putative lipid-binding domain. Three hyperlipoproteinemic probands were carriers of the APOE*2(Va1236[r arrow]Glu) allele, the APOE*3(Cys112-Arg; Arg251[r arrow]Gly) allele, or the APOE*1(Arg158[r arrow]Cys; Leu252[r arrow]Glu) allele. DGGE of the region encoding the receptor-binding domain was useful for haplotyping the mutations at codons 112 and 158. Family studies failed to demonstrate cosegregation between the new mutations and severe hyperlipoproteinemia, although a number of carriers for the APOE*3(Cys112[r arrow]Arg; Arg251[r arrow]Gly) allele and the APOE*1(Arg158-Cys; Leu252[r arrow]Glu) allele expressed hypertriglyceridemia and/ or hypercholesterolemia. Two other mutant alleles, APOE*4[sup [minus]] (Cys112[r arrow]Arg; Arg274[r arrow]His) and APOE*4[sup +] (Ser296[r arrow]Arg), were found in normolipidemic probands. The lack of cosegregation of these new mutations with severe hyperlipoproteinemia suggests that these mutations do not exert a dominant effect on the functioning of apoE. 41 refs., 5 figs., 1 tab.},
doi = {},
url = {https://www.osti.gov/biblio/6220291}, journal = {American Journal of Human Genetics; (United States)},
issn = {0002-9297},
number = ,
volume = 52:5,
place = {United States},
year = {Sat May 01 00:00:00 EDT 1993},
month = {Sat May 01 00:00:00 EDT 1993}
}