Prodynorphin promoter SNP associated with alcohol dependence forms noncanonical AP-1 binding site that may influence gene expression in human brain
2011 (English)In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1385, 18-25 p.Article in journal (Refereed) Published
Single nucleotide polymorphism (rs1997794) in promoter of the prodynorphin gene (PDYN) associated with alcohol-dependence may impact PDYN transcription in human brain. To address this hypothesis we analyzed PDYN mRNA levels in the dorsolateral prefrontal cortex (dl-PFC) and hippocampus, both involved in cognitive control of addictive behavior and PDYN promoter SNP genotype in alcohol-dependent and control human subjects. The principal component analysis suggested that PDYN expression in the dl-PFC may be related to alcoholism, while in the hippocampus may depend on the genotype. We also demonstrated that the T, low risk SNP allele resides within noncanonical AP-1-binding element that may be targeted by JUND and FOSS proteins, the dominant AP-1 constituents in the human brain. The T to C transition abrogated AP-1 binding. The impact of genetic variations on PDYN transcription may be relevant for diverse adaptive responses of this gene to alcohol.
Place, publisher, year, edition, pages
2011. Vol. 1385, 18-25 p.
Alcohol dependence, Endogenous opioid system, Prodynorphin, Gene polymorphism
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-151563DOI: 10.1016/j.brainres.2011.02.042ISI: 000289810800003PubMedID: 21338584OAI: oai:DiVA.org:uu-151563DiVA: diva2:410428