Electrophoretic screening for human apolipoprotein C-II variants: repeated identification of apolipoprotein C-II(K19T).
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 wild-type 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) cause hypertriglyceridemia in the presence of additional as yet unidentified environmental and/or genetic factors.
Wiebusch
H
H
Institut für Arterioskleroseforschung, Universität Münster, Germany.
Nofer
J R
JR
von Eckardstein
A
A
Funke
H
H
Wahrburg
U
U
Martin
H
H
Köhler
E
E
Assmann
G
G
D000328:Adult; D000595:Amino Acid Sequence; D053304:Apolipoprotein C-II; D001056:Apolipoproteins C / Q000097:blood* / Q000737:chemistry / Q000235:genetics*; D001483:Base Sequence; D014644:Genetic Variation; D006579:Heterozygote; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics; D015228:Hypertriglyceridemia / Q000235:genetics; D007525:Isoelectric Focusing; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data
D053304:Apolipoprotein C-II; D001056:Apolipoproteins C; C050929:apolipoprotein C-II (Toronto)