Characterization of five new mutants in the carboxyl-terminal domain of human apolipoprotein E: No cosegregation with severe hyperlipidemia
- Leiden Univ. (Netherlands)
- Univ. Hospital, Leiden (Netherlands)
- Westfalische Wilhelms-Universitaet, Muester (Germany)
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.
- OSTI ID:
- 6220291
- Journal Information:
- American Journal of Human Genetics; (United States), Vol. 52:5; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
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