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Published on: April 15, 2015
Prodynorphin promoter SNP associated with alcohol dependence forms noncanonical AP-1 binding site that may influence
Malik Mumtaz Taqi1, Igor Bazov, Hiroyuki Watanabe
1Division of Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences, Uppsala University, Box 591, 751 24, Uppsala, Sweden. mumtaz.malik@farmbio.uu.se
Abstract:
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.
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