Exact localization of the familial dysbetalipoproteinemia associated HpaI restriction site in the promoter region of the APOC1 gene.

An HpaI restriction fragment length polymorphism (RFLP) in the APOE-C1-C2 gene cluster on chromosome 19 is strongly associated with familial dysbetalipoproteinemia (type III hyperlipoproteinemia). Recently we localized this polymorphic HpaI site between the APOE and APOC1 genes. In the present paper we show by molecular cloning and sequencing that the polymorphic HpaI site is located 317 bp upstream of the transcription initiation site of the APOC1 gene. Overlapping cosmid clones allowed the construction of a detailed restriction map of the gene cluster, showing the APOC2 gene to be located 15 kb downstream of the APOC1 pseudogene.