Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6264949 | Brain Research | 2011 | 8 Pages |
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 FOSB 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.
Research HighlightsâºPDYN SNP associated with alcoholism impacts gene expression in human hippocampus. âºLow risk T allele of PDYN promoter SNP forms a noncanonical AP-1-binding element. âºThe T allele is targeted by the JUND and FOSB proteins in the human brain. âºThe T to C transition abrogated AP-1 binding.