Ten allelic apolipoprotein[a] 5' flanking fragments exhibit comparable promoter activities in HepG2 cells.
Plasma levels of the atherogenic lipoprotein[a] represent a quantitative genetic trait that is primarily controlled by the polymorphic apolipoprotein[a] locus on chromosome 6q. The more than 1000-fold variation in lipoprotein[a] plasma levels is explained to a large extent by a remarkable size polymorphism of the apolipoprotein[a] gene which is translated into apolipoprotein[a] isoforms and by unidentified sequence variation in apo[a]. In a recent report, sequence variation in a 1.5 kb fragment from the 5' flanking region of the apolipoprotein[a] gene was associated with different promoter activities, which led to the suggestion that transcriptional control of the apolipoprotein[a] gene might contribute significantly to lipoprotein[a] plasma levels. We have used a reporter gene assay to compare the promoter activities of these 1.5 kb fragments which were cloned from ten well-characterized apolipoprotein[a] alleles. These ten allelic apolipoprotein[a] fragments revealed, despite the same sequence variation as previously reported, comparable and relatively weak promoter activities in HepG2 hepatocarcinoma cells. Promoter activity for the same fragment in non-liver cells and the identification of a liver cell-specific DNaseI hypersensitive site 3 kb upstream from the ATG start codon suggest that longer fragments must be used in order to analyze the transcriptional regulation of the apolipoprotein[a] gene.
Bopp
S
S
Department of Molecular Biology, Boehringer Mannheim GmbH, Germany.
Köchl
S
S
Acquati
F
F
Magnaghi
P
P
Pethö-Schramm
A
A
Kraft
H G
HG
Utermann
G
G
Müller
H J
HJ
Taramelli
R
R
D000483:Alleles; D001054:Apolipoproteins A / Q000235:genetics*; D001483:Base Sequence; D003001:Cloning, Molecular; D016521:Electrophoresis, Gel, Pulsed-Field; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D014644:Genetic Variation; D006579:Heterozygote; D006801:Humans; D015151:Immunoblotting; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D014162:Transfection; D014407:Tumor Cells, Cultured
D001054:Apolipoproteins A