ALLELIC POLYMORPHISMS IN THE TRANSCRIPTIONAL REGULATORY REGION OF APOLIPOPROTEIN-E GENE

In this work, we explored the existence of genetic variants within the apolipoprotein E gene transcriptional regulatory region, using a dena turing gradient gel electrophoresis screening of a region comprising n ucleotides -1017 to +406. Upon a population study, three new polymorph ic sites (-491, -427 and -219) and two mutations were found, Functiona l effects of the polymorphisms, assayed by transient transfection and electrophoretic mobility shift assays in a human hepatoma cell Line, s howed that polymorphisms at sites -491 and -219 of the APOE promoter p roduce variations in the transcriptional activity of the gene, most pr obably through differential binding of nuclear proteins. (C) 1998 Fede ration of European Biochemical Societies.