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Electrophoretic screening for human apolipoprotein C-II variants: repeated identification of apolipoprotein C-II(K19T)

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Abstract

Screening for apolipoprotein (apo) C-II variants in the plasma of 400 students, 600 patients of a cardiological rehabilitation center, and 1200 patients of an outpatient lipid clinic by isoelectric focusing and subsequent anti-apo C-II immunoblotting led to the identification of four individuals whose plasma samples contained an apo C-II isoform with an abnormal isoelectric point. In all cases direct sequencing of PCR-amplified DNA assessed a heterozygous A to C transversion in codon 19 of the apo C-II gene which leads to the replacement of lysine with threonine. Two of the four index patients presented with moderate hypertriglyceridemia; one suffered from severe hyperlipidemia, with triglyceride levels ranging between 180 and 1900 mg/dl, depending on dietary changes. Sequencing of this proband's lipoprotein lipase gene showed no alteration compared to the wildtype sequence. A study in his family revealed that heterozygosity for apo C-II(K19T) is not associated with differences in mean lipid and lipoprotein concentrations. In conclusion, apo C-II(K19T) occurs in Germany at a frequency of approximately 1 in 550. Although this variant is not sufficient to cause hypertriglyceridemia, it may be possible that apo C-II(K19T) causes hypertriglyceridemia in the presence of additional as yet unidentified environmental and/or genetic factors.

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Abbreviations

Apo :

Apolipoprotein

HDL :

High-density lipoprotein

HTGL :

Hepatic triglyceride lipase

IEF :

Isoelectric focusing

LPL :

Lipoprotein lipase

PCR :

Polymerase chain reaction

VLDL :

Very low density lipoproteins

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Authors and Affiliations

  1. Institut für Arterioskleroseforschung, Universität Münster, Domagkstrasse 3, D-48129, Münster, Germany

    H. Wiebusch, U. Wahrburg & H. Martin

  2. Institut für Arterioskleroseforschung, Universität Münster, Domagkstrasse 3, Germany

    G. Assmann

  3. Institut für Klinische Chemie und Laboratoriumsmedizin, Zentrallaboratorium Westfälische Wilhelms-Universität, Albert-Schweizer-Strasse 33, D-48129, Münster, Germany

    G. Assmann

  4. Institut für Klinische Chemie und Laboratoriumsmedizin, Zentrallaboratorium, Westfälische Wilhelms-Universität, Albert-Schweizer-Strasse 33, D-48129, Münster, Germany

    J.-R. Nofer, A. von Eckardstein, H. Funke & U. Wahrburg

  5. Salzetalklinik der LVA, Alte Vlothoer Strasse 1, D-32066, Bad Salzuflen, Germany

    E. Köhler

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  1. H. Wiebusch
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  2. J.-R. Nofer
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  3. A. von Eckardstein
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  4. H. Funke
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  6. H. Martin
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  7. E. Köhler
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  8. G. Assmann
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Wiebusch, H., Nofer, JR., von Eckardstein, A. et al. Electrophoretic screening for human apolipoprotein C-II variants: repeated identification of apolipoprotein C-II(K19T). J Mol Med 73, 373–378 (1995). https://doi.org/10.1007/BF00192889

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  • DOI: https://doi.org/10.1007/BF00192889

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