Zimprich A, Kraus J, Wöltje M, Mayer P, Rauch E, Höllt V
Institute for Pharmacology and Toxicology, Otto-von-Guericke University, Magdeburg, Germany.
J Neurochem. 2000 Feb;74(2):472-7. doi: 10.1046/j.1471-4159.2000.740472.x.
Prodynorphin, the precursor of the dynorphin opioid peptides, has been shown to play an important role in several aspects of human diseases and complex 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 human prodynorphin gene and to relate these polymorphisms to prodynorphin gene expression. Within the core promoter region, a 68-bp sequence was found to occur as a polymorphic element, either singular or as tandemly repeated element two, three, or four times. This 68-bp repeat element contains an AP-1 transcription factor binding site as demonstrated by electrophoretic mobility shift assay. Reporter gene assays were performed and provided evidence for allele dependent different promoter activity. Dynorphin was found to be involved in many pathophysiological processes so that the described prodynorphin alleles may correlate with the occurrence of several diseases, for example, drug addiction. However, prodynorphin allelic distributions were not significantly different in heroin addicts and control subjects.
强啡肽原是强啡肽类阿片肽的前体，已被证明在人类疾病和复杂性状的多个方面发挥重要作用，如药物滥用、癫痫和情绪障碍。本研究的目的是鉴定人类强啡肽原基因5'调控区的多态性，并将这些多态性与强啡肽原基因表达相关联。在核心启动子区域，发现一个68bp的序列作为多态性元件存在，它可以单独出现，也可以作为串联重复元件出现两次、三次或四次。如电泳迁移率变动分析所示，这个68bp的重复元件包含一个AP-1转录因子结合位点。进行了报告基因分析，并提供了等位基因依赖性不同启动子活性的证据。强啡肽被发现参与许多病理生理过程，因此所描述的强啡肽原等位基因可能与几种疾病的发生相关，例如药物成瘾。然而，海洛因成瘾者和对照受试者的强啡肽原等位基因分布没有显著差异。
