An allelic variation in the human prodynorphin gene promoter alters stimulus-induced expression

Prodynorphin, the precursor of the dynorphin opioid peptides, has been show n to play an important role in several aspects of human diseases and comple x traits, e.g,, drug abuse, epilepsy, and mood disorders. The objective of this study was to identify polymorphisms in the 5' control region of the hu man prodynorphin gene and to relate these polymorphisms to prodynorphin gen e expression. Within the core promoter region, a 68-bp sequence was found t o occur as a polymorphic element, either singular or as tandemly repeated e lement two, three, or four times. This 68-bp repeat element contains an AP- 1 transcription factor binding site as demonstrated by electrophoretic mobi lity shift assay. Reporter gene assays were performed and provided evidence for allele dependent different promoter activity. Dynorphin was found to b e involved in many pathophysiological processes so that the described prody norphin alleles may correlate with the occurrence of several diseases, for example, drug addiction. However, prodynorphin allelic distributions were n ot significantly different in heroin addicts and control subjects.