Here is described a novel gene, the interferon inducible gene 12 (ISG12,
IFI27), that interacts with nuclear receptors and enhances nuclear export
of such transcription factors. As a consequence, the transcriptional
activities of these nuclear receptors are decreased. As examples effects
on NR4A1 and PPARa and PPARg are given. When ISG12 is absent as in ISG12
deficient mice transcriptional activities of these nuclear receptors are
not impaired and their protective effects are fully appreciated.
Consistently, ISG12 deficient mice are resistant to restenosis upon
carotid artery ligation and to endotoxin induced death. Human genetics
studies indicate the importance of ISG12 where the inventors could show a
strong association between an intronic ISG12 SNP and the presence of
hypercholesterolemia, diabetes type 2 and stroke. ISG12 is therefore a
target for novel therapeutic strategies for the treatment of vascular
diseases.