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Brain Res. 2011 Apr 18;1385:18-25. doi: 10.1016/j.brainres.2011.02.042. Epub 2011 Feb 19.

Prodynorphin promoter SNP associated with alcohol dependence forms noncanonical AP-1 binding site that may influence gene expression in human brain.

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  • 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.

Copyright © 2011 Elsevier B.V. All rights reserved.

PMID:
21338584
[PubMed - indexed for MEDLINE]
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